FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Biomolecules2022; 12(10); doi: 10.3390/biom12101525

Cyclosporine A Delivery Platform for Veterinary Ophthalmology-A New Concept for Advanced Ophthalmology.

Abstract: Cyclosporine A (CsA) is a selective and reversible immunosuppressant agent that is widely used as a medication for a wide spectrum of diseases in humans such as graft versus host disease, non-infectious uveitis, rheumatoid arthritis, psoriasis, and atopic dermatitis. Furthermore, the CsA is used to treat keratoconjunctivitis sicca, chronic superficial keratitis, immune-mediated keratitis and equine recurrent uveitis in animals. The selective activity of Cyclosporine A (CsA) was demonstrated to be an immunomodulation characteristic of T-lymphocyte proliferation and inhibits cytokine gene expression. Moreover, the lipophilic characteristics with poor bioavailability and low solubility in water, besides the side effects, force the need to develop new formulations and devices that will provide adequate penetration into the anterior and posterior segments of the eye. This review aims to summarize the effectiveness and safety of cyclosporine A delivery platforms in veterinary ophthalmology.
Get Full Text
Publication Date: 2022-10-20 PubMed ID: 36291734PubMed Central: PMC9599649DOI: 10.3390/biom12101525Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This article discusses the use of Cyclosporine A (CsA), a drug known for its immunosuppressive properties, in veterinary ophthalmology and the need for development of innovative delivery methods for this medication due to its nature of properties.

Introduction to Cyclosporine A (CsA)

  • Cyclosporine A is considered as one of the prominent immunosuppressive drugs.
  • Its widespread application encompasses several diseases, primarily driven by its ability to selectively and reversibly suppress the immune system.
  • Its usage is not limited to human diseases such as graft versus host disease, non-infectious uveitis, rheumatoid arthritis, psoriasis, and atopic dermatitis, it also finds significance in treating multiple eye conditions in animals.

Applications in Veterinary Ophthalmology

  • The usage of CsA extends extensively in veterinary medicine.
  • Particularly in ophthalmology, it helps in treating numerous eye conditions, including keratoconjunctivitis sicca, chronic superficial keratitis, immune-mediated keratitis, and equine recurrent uveitis.
  • These diseases characteristically show an overactive or misplaced immune response, thus CsA helps in moderating these responses and aiding in the treatment.

Immunomodulatory Properties of CsA

  • The primary reason behind CsA’s versatility is its selective immunosuppression.
  • Essentially, it moderates the immune system by inhibiting T-lymphocyte proliferation and suppressing the expression of certain genes that produce cytokines, the substances that help in immune system communication.
  • The specificity of the immunomodulatory effects is what makes it preferred for a wide array of diseases.

Lipophilic Characteristics and Delivery Challenges

  • Despite its extensive applications, CsA does present a few challenges.
  • Primarily, it’s a lipophilic substance, which means that it dissolves in fat but has a low solubility in water.
  • Consequently, this property equates to poor bioavailability, i.e., a lower proportion of the drug reaches the site of action when administered.
  • Furthermore, the side effects of CsA treatment necessitate the development of new delivery formulations to ensure the required dosage reach the eye tissues effectively.

Considerations for Future Research and Development

  • Central to this review is the emphasis on exploring advanced delivery methods for CsA.
  • The objective is to yield better penetration into the anterior and posterior sections of the eye, while reducing side effects.
  • This focus is driven by the desire to maintain CsA’s remarkable utility in veterinary ophthalmology while confronting the challenges that come with its use.

Cite This Article

APA
Padjasek M, Qasem B, Cisło-Pakuluk A, Marycz K. (2022). Cyclosporine A Delivery Platform for Veterinary Ophthalmology-A New Concept for Advanced Ophthalmology. Biomolecules, 12(10). https://doi.org/10.3390/biom12101525

Publication

Biomolecules
ISSN: 2218-273X
NlmUniqueID: 101596414
Country: Switzerland
Language: English
Volume: 12
Issue: 10

Researcher Affiliations

Padjasek, Martyna
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
Qasem, Badr
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
Cisło-Pakuluk, Anna
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
Marycz, Krzysztof
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, The University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.

MeSH Terms

  • Humans
  • Horses
  • Animals
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Ophthalmology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Uveitis / drug therapy
  • Keratitis / drug therapy
  • Cytokines
  • Water

Conflict of Interest Statement

Authors declare no conflicts of interest.

References

This article includes 94 references
  1. Colombo D, Ammirati E. Cyclosporine in transplantation–A history of converging timelines.. J. Biol. Regul. Homeost. Agents 2011;25:493–504.
    pubmed: 22217983
  2. Borel J.F. History of the discovery of cyclosporin and of its early pharmacological development.. Wien. Klin. Wochenschr. 2002;114:433–437.
    pubmed: 12422576
  3. Borel J.F. Comparative study of in vitro and in vivo drug effects on cell-mediated cytotoxicity.. Immunology 1976;31:631–641.
    pmc: PMC1445361pubmed: 824198
  4. Faulds D, Goa K.L, Benfield P. Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders.. Drugs 1993;45:953–1040.
    doi: 10.2165/00003495-199345060-00007pubmed: 7691501google scholar: lookup
  5. Teimouri A, Ahmadi S.R, Anavri Ardakani S, Foroughian M. Cyclosporine-A-Based Immunosuppressive Therapy-Induced Neurotoxicity: A Case Report.. Open Access Emerg. Med. 2020;12:93–97.
    doi: 10.2147/OAEM.S241501pmc: PMC7197938pubmed: 32431553google scholar: lookup
  6. Shi W, Chen M, Xie L, Liu M, Gao H, Wang T, Wu X, Zhao J. A novel cyclosporine a drug-delivery system for prevention of human corneal rejection after high-risk keratoplasty: A clinical study.. Ophthalmology 2013;120:695–702.
    doi: 10.1016/j.ophtha.2012.09.035pubmed: 23246118google scholar: lookup
  7. Zhang T, Li Z, Liu T, Li S, Gao H, Wei C, Shi W. Cyclosporine a drug-delivery system for high-risk penetrating keratoplasty: Stabilizing the intraocular immune microenvironment.. PLoS ONE 2018;13:e0196571.
    doi: 10.1371/journal.pone.0196571pmc: PMC5937766pubmed: 29734357google scholar: lookup
  8. Eperon S, Rodriguez-Aller M, Balaskas K, Gurny R, Guex-Crosier Y. A new drug delivery system inhibits uveitis in an animal model after cataract surgery.. Int. J. Pharm. 2013;443:254–261.
    doi: 10.1016/j.ijpharm.2012.12.033pubmed: 23291445google scholar: lookup
  9. Teng H, Zhang H, Tian F, Gu H.Q, Liu X, Sun J. The study of cyclosporin A modified intraocular lens preventing posterior capsular opacification in rabbit eyes.. Zhonghua Yan Ke Za Zhi 2016;52:110–116.
    doi: 10.3760/cma.j.issn.0412-4081.2016.02pubmed: 26906706google scholar: lookup
  10. Teng H, Sun J, Wen K, Han G, Tian F. Observation of cyclosporin A: Sustained release intraocular lens implantation in rabbit eyes.. Curr. Eye Res. 2022;47:1508–1515.
    doi: 10.1080/02713683.2022.2110598pubmed: 35947019google scholar: lookup
  11. Lu D, Han Y, Liu D, Chen S, Qie J, Qu J, Lin Q. Centrifugally concentric ring-patterned drug-loaded polymeric coating as an intraocular lens surface modification for efficient prevention of posterior capsular opacification.. Acta Biomater. 2022;138:327–341.
    doi: 10.1016/j.actbio.2021.11.018pubmed: 34800717google scholar: lookup
  12. Lyu N, Zhao Y, Xiang J, Fan X, Huang C, Sun X, Xu J, Xu Z.P, Sun J. Inhibiting corneal neovascularization by sustainably releasing anti-VEGF and anti-inflammation drugs from silica-thermogel nanohybrids.. Mater. Sci. Eng. C Mater. Biol. Appl. 2021;128:112274.
    doi: 10.1016/j.msec.2021.112274pubmed: 34474833google scholar: lookup
  13. Dai Z, Yu X, Hong J, Liu X, Sun J, Sun X. Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis.. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;66:206–214.
    doi: 10.1016/j.msec.2016.04.077pubmed: 27207056google scholar: lookup
  14. Velluto D, Demurtas D, Hubbell J.A. PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release: Cyclosporin A as an example.. Mol. Pharm. 2008;5:632–642.
    doi: 10.1021/mp7001297pubmed: 18547055google scholar: lookup
  15. Czogalla A. Oral cyclosporine A—The current picture of its liposomal and other delivery systems.. Cell. Mol. Biol. Lett. 2009;14:139–152.
    doi: 10.2478/s11658-008-0041-6pmc: PMC6275704pubmed: 19005620google scholar: lookup
  16. Bravo González R.C, Huwyler J, Walter I, Mountfield R, Bittner B. Improved oral bioavailability of cyclosporin A in male Wistar rats. Comparison of a Solutol HS 15 containing self-dispersing formulation and a microsuspension.. Int. J. Pharm. 2002;245:143–151.
    doi: 10.1016/S0378-5173(02)00339-3pubmed: 12270251google scholar: lookup
  17. Rose S, Jenner P, Marsden C.D. Peripheral pharmacokinetic handling and metabolism of L-dopa in the rat: The effect of route of administration and carbidopa pretreatment.. J. Pharm. Pharmacol. 1991;43:325–330.
    doi: 10.1111/j.2042-7158.1991.tb06698.xpubmed: 1680174google scholar: lookup
  18. Dubey P, Barker S.A, Craig D.Q.M. Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution.. ACS Omega 2020;5:1003–1013.
    doi: 10.1021/acsomega.9b02616pmc: PMC6977102pubmed: 31984256google scholar: lookup
  19. Kelly P.A, Wang H, Napoli K.L, Kahan B.D, Strobel H.W. Metabolism of cyclosporine by cytochromes P450 3A9 and 3A4.. Eur. J. Drug Metab. Pharmacokinet. 1999;24:321–328.
    doi: 10.1007/BF03190040pubmed: 10892895google scholar: lookup
  20. Price D.A, Eng H, Farley K.A, Goetz G.H, Huang Y, Jiao Z, Kalgutkar A.S, Kablaoui N.M, Khunte B, Liras S. Comparative Pharmacokinetic Profile of Cyclosporine (CsA) with a Decapeptide and a Linear Analogue.. Org. Biomol. Chem. 2017;15:2501–2506.
    doi: 10.1039/C7OB00096Kpubmed: 28266673google scholar: lookup
  21. Marshall G.R, Beusen D.D, Nikiforovich G.V. 5–Peptide Conformation: Stability and Dynamics.. Peptides 1995;pp. 193–245.
    doi: 10.1016/B978-012310920-0/50006-1google scholar: lookup
  22. Patel D, Wairkar S. Recent advances in cyclosporine drug delivery: Challenges and opportunities.. Drug Deliv. Transl. Res. 2019;9:1067–1081.
    doi: 10.1007/s13346-019-00650-1pubmed: 31144214google scholar: lookup
  23. Clipstone N.A, Crabtree G.R. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation.. Nature 1992;357:695–697.
    doi: 10.1038/357695a0pubmed: 1377362google scholar: lookup
  24. Matsuda S, Koyasu S. Mechanisms of action of cyclosporine.. Immunopharmacology 2000;47:119–125.
    doi: 10.1016/S0162-3109(00)00192-2pubmed: 10878286google scholar: lookup
  25. Matsuda S, Moriguchi T, Koyasu S, Nishida E. T lymphocyte activation signals for interleukin-2 production involve activation of MKK6-p38 and MKK7-SAPK/JNK signaling pathways sensitive to cyclosporin A.. J. Biol. Chem. 1998;273:12378–12382.
    doi: 10.1074/jbc.273.20.12378pubmed: 9575191google scholar: lookup
  26. Karin M, Delhase M. JNK or IKK, AP-1 or NF-kappaB, which are the targets for MEK kinase 1 action?. Proc. Natl. Acad. Sci. USA 1998;95:9067–9069.
    doi: 10.1073/pnas.95.16.9067pmc: PMC33875pubmed: 9689033google scholar: lookup
  27. Collins T.L, Deckert M, Altman A. Views on Vav.. Immunol. Today 1997;18:221–225.
    doi: 10.1016/S0167-5699(97)01037-2pubmed: 9153953google scholar: lookup
  28. Matsuda S, Shibasaki F, Takehana K, Mori H, Nishida E, Koyasu S. Two distinct action mechanisms of immunophilin-ligand complexes for the blockade of T-cell activation.. EMBO Rep. 2000;1:428–434.
    doi: 10.1093/embo-reports/kvd090pmc: PMC1083763pubmed: 11258483google scholar: lookup
  29. Agarwal P, Rupenthal I.D. Modern approaches to the ocular delivery of cyclosporine A.. Drug Discov. Today 2016;21:977–988.
    doi: 10.1016/j.drudis.2016.04.002pubmed: 27080149google scholar: lookup
  30. Nussenblatt R.B, Palestine A.G. Cyclosporine: Immunology, pharmacology and therapeutic uses.. Surv. Ophthalmol. 1986;31:159–169.
    doi: 10.1016/0039-6257(86)90035-4pubmed: 3544293google scholar: lookup
  31. Lallemand F, Felt-Baeyens O, Besseghir K, Behar-Cohen F, Gurny R. Cyclosporine A delivery to the eye: A pharmaceutical challenge.. Eur. J. Pharm. Biopharm. 2003;56:307–318.
    doi: 10.1016/S0939-6411(03)00138-3pubmed: 14602172google scholar: lookup
  32. Mihatsch M.J, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V, Ryffel B. The side-effects of ciclosporine-A and tacrolimus.. Clin. Nephrol. 1998;49:356–363.
    pubmed: 9696431
  33. Williams D.L. A comparative approach to topical cyclosporine therapy.. Pt 4Eye 1997;11:453–464.
    doi: 10.1038/eye.1997.126pubmed: 9425407google scholar: lookup
  34. Utine C.A, Stern M, Akpek E.K. Clinical review: Topical ophthalmic use of cyclosporin A.. Ocul. Immunol. Inflamm. 2010;18:352–361.
    doi: 10.3109/09273948.2010.498657pubmed: 20735287google scholar: lookup
  35. Hessen M, Akpek E.K. Ocular graft-versus-host disease.. Curr. Opin. Allergy Clin. Immunol. 2012;12:540–547.
    doi: 10.1097/ACI.0b013e328357b4b9pubmed: 22892710google scholar: lookup
  36. Prabhu S.S, Shtein R.M, Michelotti M.M, Cooney T.M. Topical cyclosporine A 0.05% for recurrent anterior uveitis.. Br. J. Ophthalmol. 2016;100:345–347.
    doi: 10.1136/bjophthalmol-2015-307251pubmed: 26286822google scholar: lookup
  37. Singhal D, Sahay P, Maharana P.K, Raj N, Sharma N, Titiyal J.S. Vernal Keratoconjunctivitis.. Surv. Ophthalmol. 2019;64:289–311.
    doi: 10.1016/j.survophthal.2018.12.001pubmed: 30550738google scholar: lookup
  38. Gilger B.C, Michau T.M. Equine recurrent uveitis: New methods of management.. Vet. Clin. N. Am. Equine Pract. 2004;20:417–427.
    doi: 10.1016/j.cveq.2004.04.010pubmed: 15271431google scholar: lookup
  39. Matthews A, Gilger B.C. Equine immune-mediated keratopathies.. Vet. Ophthalmol. 2009;12((Suppl. 1)):10–16.
    doi: 10.1111/j.1463-5224.2009.00740.xpubmed: 19891646google scholar: lookup
  40. Pearson P.A, Jaffe G.J, Martin D.F, Cordahi G.J, Grossniklaus H, Schmeisser E.T, Ashton P. Evaluation of a delivery system providing long-term release of cyclosporine.. Arch. Ophthalmol. 1996;114:311–317.
    doi: 10.1001/archopht.1996.01100130307014pubmed: 8600892google scholar: lookup
  41. Smith T.J, Pearson P.A, Blandford D.L, Brown J.D, Goins K.A, Hollins J.L, Schmeisser E.T, Glavinos P, Baldwin L.B, Ashton P. Intravitreal sustained-release ganciclovir.. Arch. Ophthalmol. 1992;110:255–258.
    doi: 10.1001/archopht.1992.01080140111037pubmed: 1310588google scholar: lookup
  42. Enyedi L.B, Pearson P.A, Ashton P, Jaffe G.J. An intravitreal device providing sustained release of cyclosporine and dexamethasone.. Curr. Eye Res. 1996;15:549–557.
    doi: 10.3109/02713689609000766pubmed: 8670756google scholar: lookup
  43. Jaffe G.J, Yang C.S, Wang X.C, Cousins S.W, Gallemore R.P, Ashton P. Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis.. Ophthalmology 1998;105:46–56.
    doi: 10.1016/S0161-6420(98)91176-9pubmed: 9442778google scholar: lookup
  44. Izci C, Celik I, Alkan F, Ogurtan Z, Ceylan C, Sur E, Ozkan Y. Histologic characteristics and local cellular immunity of the gland of the third eyelid after topical ophthalmic administration of 2% cyclosporine for treatment of dogs with keratoconjunctivitis sicca.. Am. J. Vet. Res. 2002;63:688–694.
    doi: 10.2460/ajvr.2002.63.688pubmed: 12013470google scholar: lookup
  45. Kaswan R.L, Salisbury M.A, Ward D.A. Spontaneous canine keratoconjunctivitis sicca. A useful model for human keratoconjunctivitis sicca: Treatment with cyclosporine eye drops.. Arch. Ophthalmol. 1989;107:1210–1216.
    doi: 10.1001/archopht.1989.01070020276038pubmed: 2757551google scholar: lookup
  46. Kaswan R.L, Salisbury M.A. A new perspective on canine keratoconjunctivitis sicca. Treatment with ophthalmic cyclosporine.. Vet. Clin. N. Am. Small Anim. Pract. 1990;20:583–613.
    doi: 10.1016/S0195-5616(90)50052-2pubmed: 2194349google scholar: lookup
  47. Bittencourt M.K.W, Barros M.A, Martins J.F.P, Vasconcellos J.P.C, Morais B.P, Pompeia C, Bittencourt M.D, Evangelho K.D.S, Kerkis I, Wenceslau C.V. Allogeneic mesenchymal stem cell transplantation in dogs with keratoconjunctivitis sicca.. Cell Med. 2016;8:63–77.
    doi: 10.3727/215517916X693366pmc: PMC5165646pubmed: 28003932google scholar: lookup
  48. Dodi P.L. Immune-mediated keratoconjunctivitis sicca in dogs: Current perspectives on management.. Vet. Med. Res. Rep. 2015;6:341–347.
    doi: 10.2147/VMRR.S66705pmc: PMC6067592pubmed: 30101119google scholar: lookup
  49. Williams D.L, Tighe A.A. Immunohistochemical evaluation of lymphocyte populations in the nictitans glands of normal dogs and dogs with keratoconjunctivitis sicca.. Open Vet. J. 2018;8:47–52.
    doi: 10.4314/ovj.v8i1.8pmc: PMC5806667pubmed: 29445621google scholar: lookup
  50. Kim H, Csaky K.G, Gilger B.C, Dunn J.P, Lee S.S, Tremblay M, de Monasterio F, Tansey G, Yuan P, Bungay P.M. Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease.. Investig. Ophthalmol. Vis. Sci. 2005;46:655–662.
    doi: 10.1167/iovs.04-1076pubmed: 15671296google scholar: lookup
  51. Acton A.E, Beale A.B, Gilger B.C, Stoskopf M.K. Sustained release cyclosporine therapy for bilateral keratoconjunctivitis sicca in a red wolf (Canis rufus). J. Zoo Wildl. Med. 2006;37:562–564.
    doi: 10.1638/06-021.1pubmed: 17315447google scholar: lookup
  52. Lee S.S, Kim H, Wang N.S, Bungay P.M, Gilger B.C, Yuan P, Kim J, Csaky K.G, Robinson M.R. A pharmacokinetic and safety evaluation of an episcleral cyclosporine implant for potential use in high-risk keratoplasty rejection.. Investig. Ophthalmol. Vis. Sci. 2007;48:2023–2029.
    doi: 10.1167/iovs.06-0985pubmed: 17460256google scholar: lookup
  53. Barachetti L, Rampazzo A, Mortellaro C.M, Scevola S, Gilger B.C. Use of episcleral cyclosporine implants in dogs with keratoconjunctivitis sicca: Pilot study.. Vet. Ophthalmol. 2015;18:234–241.
    doi: 10.1111/vop.12173pubmed: 24799029google scholar: lookup
  54. Choi J.H, Li Y, Jin R, Shrestha T, Choi J.S, Lee W.J, Moon M.J, Ju H.T, Choi W, Yoon K.C. The Efficiency of Cyclosporine A-Eluting Contact Lenses for the Treatment of Dry Eye.. Curr. Eye Res. 2019;44:486–496.
    doi: 10.1080/02713683.2018.1563702pubmed: 30580651google scholar: lookup
  55. Soluri A, Hui A, Jones L. Delivery of ketotifen fumarate by commercial contact lens materials.. Optom. Vis. Sci. 2012;89:1140–1149.
    doi: 10.1097/OPX.0b013e3182639dc8pubmed: 22773177google scholar: lookup
  56. Guzman-Aranguez A, Colligris B, Pintor J. Contact lenses: Promising devices for ocular drug delivery.. J. Ocul. Pharmacol. Ther. 2013;29:189–199.
    doi: 10.1089/jop.2012.0212pubmed: 23215541google scholar: lookup
  57. Maulvi F.A, Shaikh A.A, Lakdawala D.H, Desai A.R, Pandya M.M, Singhania S.S, Vaidya R.J, Ranch K.M, Vyas B.A, Shah D.O. Design and optimization of a novel implantation technology in contact lenses for the treatment of dry eye syndrome: In vitro and in vivo evaluation.. Acta Biomater. 2017;53:211–221.
    doi: 10.1016/j.actbio.2017.01.063pubmed: 28131945google scholar: lookup
  58. Chandasana H, Prasad Y.D, Chhonker Y.S, Chaitanya T.K, Mishra N.N, Mitra K, Shukla P.K, Bhatta R.S. Corneal targeted nanoparticles for sustained natamycin delivery and their PK/PD indices: An approach to reduce dose and dosing frequency.. Int. J. Pharm. 2014;477:317–325.
    doi: 10.1016/j.ijpharm.2014.10.035pubmed: 25455776google scholar: lookup
  59. Jung H.J, Abou-Jaoude M, Carbia B.E, Plummer C, Chauhan A. Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses.. J. Control. Release. 2013;165:82–89.
    doi: 10.1016/j.jconrel.2012.10.010pubmed: 23123188google scholar: lookup
  60. Shirley M. Bimatoprost implant: First approval.. Drugs Aging 2020;37:457–462.
    doi: 10.1007/s40266-020-00769-8pmc: PMC7303088pubmed: 32447639google scholar: lookup
  61. Vanslette A, Blizzard C.D, Haberman P, Tomaszewski J, Rosales C, Metzinger J.L, Goldstein M.H, Driscoll A. Pharmacokinetics of OTX-CSI, a Sustained Release Cyclosporine Intracanalicular Insert in Beagles.. Investig. Ophthalmol. Vis. Sci. 2019;60:285.
  62. Slatter D.H, Lavach J.D, Severin G.A, Young S. Uberreiter’s syndrome (chronic superficial keratitis) in dogs in the Rocky Mountain area—A study of 463 cases.. J. Small Anim. Pract. 1977;18:757–772.
    doi: 10.1111/j.1748-5827.1977.tb05852.xpubmed: 599907google scholar: lookup
  63. Andrew S.E. Immune-mediated canine and feline keratitis.. Vet. Clin. N. Am. Small Anim. Pract. 2008;38:269–290.
    doi: 10.1016/j.cvsm.2007.11.007pubmed: 18299007google scholar: lookup
  64. Bedford P.G, Longstaffe J.A. Corneal pannus (chronic superficial keratitis) in the German shepherd dog.. J. Small Anim. Pract. 1979;20:41–56.
    doi: 10.1111/j.1748-5827.1979.tb07019.xpubmed: 759720google scholar: lookup
  65. Eichenbaum J.D, Lavach J.D, Gould D.H, Severin G.A, Paulsen M.E, Jones R.L. Immunohistochemical staining patterns of canine eyes affected with chronic superficial keratitis.. Am. J. Vet. Res. 1986;47:1952–1955.
    pubmed: 3767102
  66. Williams D.L. Histological and immunohistochemical evaluation of canine chronic superficial keratitis.. Res. Vet. Sci. 1999;67:191–195.
    doi: 10.1053/rvsc.1999.0329pubmed: 10502491google scholar: lookup
  67. Williams D.L, Cribb A, Scott J.E. Proteoglycan-collagen interactions in chronic superficial keratitis in the dog.. Biochem. Soc. Trans. 1991;19:353S.
    doi: 10.1042/bst019353spubmed: 1794491google scholar: lookup
  68. Drahovska Z, Balicki I, Trbolova A, Mihalova M, Holickova M. A retrospective study of the occurrence of chronic superficial keratitis in 308 German Shepherd dogs: 1999–2010.. Pol. J. Vet. Sci. 2014;17:543–546.
    doi: 10.2478/pjvs-2014-0082pubmed: 25286670google scholar: lookup
  69. Chavkin M.J, Roberts S.M, Salman M.D, Severin G.A, Scholten N.J. Risk factors for development of chronic superficial keratitis in dogs.. J. Am. Vet. Med. Assoc. 1994;204:1630–1634.
    pubmed: 8050943
  70. Denk N, Fritsche J, Reese S. The effect of UV-blocking contact lenses as a therapy for canine chronic superficial keratitis.. Vet. Ophthalmol. 2011;14:186–194.
    doi: 10.1111/j.1463-5224.2010.00863.xpubmed: 21521443google scholar: lookup
  71. Williams D.L, Hoey A.J, Smitherman P. Comparison of topical cyclosporin and dexamethasone for the treatment of chronic superficial keratitis in dogs.. Vet. Rec. 1995;137:635–639.
    pubmed: 8693674
  72. Gilger B.C, Michau T.M, Salmon J.H. Immune-mediated keratitis in horses: 19 cases (1998–2004). Vet. Ophthalmol. 2005;8:233–239.
    doi: 10.1111/j.1463-5224.2005.00393.xpubmed: 16008702google scholar: lookup
  73. Gilger B.C, Stoppini R, Wilkie D.A, Clode A.B, Pinto N.H, Hempstead J, Gerding J, Salmon J.H. Treatment of immune-mediated keratitis in horses with episcleral silicone matrix cyclosporine delivery devices.. Vet. Ophthalmol. 2014;17((Suppl. 1)):23–30.
    doi: 10.1111/vop.12087pubmed: 23910236google scholar: lookup
  74. Sandmeyer L.S, Bauer B.S, Feng C.X, Grahn B.H. Equine recurrent uveitis in western Canadian prairie provinces: A retrospective study (2002–2015). Can. Vet. J. 2017;58:717–722.
    pmc: PMC5501119pubmed: 28698690
  75. Gerding J.C, Gilger B.C. Prognosis and impact of equine recurrent uveitis.. Equine Vet. J. 2016;48:290–298.
    doi: 10.1111/evj.12451pubmed: 25891653google scholar: lookup
  76. Kalsow C.M, Dwyer A.E, Smith A.W, Nifong T.P. Pinealitis accompanying equine recurrent uveitis.. Br. J. Ophthalmol. 1993;77:46–48.
    doi: 10.1136/bjo.77.1.46pmc: PMC504423pubmed: 8435400google scholar: lookup
  77. Deeg C.A, Ehrenhofer M, Thurau S.R, Reese S, Wildner G, Kaspers B. Immunopathology of recurrent uveitis in spontaneously diseased horses.. Exp. Eye Res. 2002;75:127–133.
    doi: 10.1006/exer.2002.2011pubmed: 12137758google scholar: lookup
  78. Malalana F, Stylianides A, McGowan C. Equine recurrent uveitis: Human and equine perspectives.. Vet. J. 2015;206:22–29.
    doi: 10.1016/j.tvjl.2015.06.017pubmed: 26188862google scholar: lookup
  79. Allbaugh R.A. Equine recurrent uveitis: A review of clinical assessment and management.. Equine Vet. Educ. 2017;29:279–288.
    doi: 10.1111/eve.12548google scholar: lookup
  80. Lorenz L, Amann B, Hirmer S, Degroote R.L, Hauck S.M, Deeg C.A. NEU1 is more abundant in uveitic retina with concomitant desialylation of retinal cells.. Glycobiology 2021;31:873–883.
    doi: 10.1093/glycob/cwab014pubmed: 33677598google scholar: lookup
  81. McMullen R.J, Fischer B.M. Medical and surgical management of equine recurrent uveitis.. Vet. Clin. N. Am. Equine Pract. 2017;33:465–481.
    doi: 10.1016/j.cveq.2017.07.003pubmed: 28985983google scholar: lookup
  82. Gilger B.C, Malok E, Stewart T, Horohov D, Ashton P, Smith T, Jaffe G.J, Allen J.B. Effect of an intravitreal cyclosporine implant on experimental uveitis in horses.. Vet. Immunol. Immunopathol. 2000;76:239–255.
    doi: 10.1016/S0165-2427(00)00219-1pubmed: 11044557google scholar: lookup
  83. Gilger B.C, Malok E, Stewart T, Ashton P, Smith T, Jaffe G.J, Allen J.B. Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A.. Vet. Ophthalmol. 2000;3:105–110.
    doi: 10.1046/j.1463-5224.2000.00117.xpubmed: 11397291google scholar: lookup
  84. Gilger B.C, Wilkie D.A, Davidson M.G, Allen J.B. Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.. Am. J. Vet. Res. 2001;62:1892–1896.
    doi: 10.2460/ajvr.2001.62.1892pubmed: 11763177google scholar: lookup
  85. Shane T.S, Martin D.F, Endopthalmitis-Gancioclovir Implant Study Group. Endophthalmitis after ganciclovir implant in patients with AIDS and cytomegalovirus retinitis.. Am. J. Ophthalmol. 2003;136:649–654.
    doi: 10.1016/S0002-9394(03)00333-7pubmed: 14516804google scholar: lookup
  86. Sakurai E, Nozaki M, Okabe K, Kunou N, Kimura H, Ogura Y. Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis.. Investig. Ophthalmol. Vis. Sci. 2003;44:4845–4852.
    doi: 10.1167/iovs.02-1228pubmed: 14578407google scholar: lookup
  87. Miyamoto H, Ogura Y, Hashizoe M, Kunou N, Honda Y, Ikada Y. Biodegradable scleral implant for intravitreal controlled release of fluconazole.. Curr. Eye Res. 1997;16:930–935.
    doi: 10.1076/ceyr.16.9.930.5042pubmed: 9288455google scholar: lookup
  88. Okabe K, Kimura H, Okabe J, Kato A, Kunou N, Ogura Y. Intraocular tissue distribution of betamethasone after intrascleral administration using a non-biodegradable sustained drug delivery device.. Investig. Ophthalmol. Vis. Sci. 2003;44:2702–2707.
    doi: 10.1167/iovs.02-0956pubmed: 12766076google scholar: lookup
  89. Okabe J, Kimura H, Kunou N, Okabe K, Kato A, Ogura Y. Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate.. Investig. Ophthalmol. Vis. Sci. 2003;44:740–744.
    doi: 10.1167/iovs.02-0375pubmed: 12556407google scholar: lookup
  90. Kato A, Kimura H, Okabe K, Okabe J, Kunou N, Ogura Y. Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant.. Investig. Ophthalmol. Vis. Sci. 2004;45:238–244.
    doi: 10.1167/iovs.02-1258pubmed: 14691179google scholar: lookup
  91. Gilger B.C, Salmon J.H, Wilkie D.A, Cruysberg L.P.J, Kim J, Hayat M, Kim H, Kim S, Yuan P, Lee S.S. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.. Investig. Ophthalmol. Vis. Sci. 2006;47:2596–2605.
    doi: 10.1167/iovs.05-1540pubmed: 16723476google scholar: lookup
  92. Cislo-Pakuluk A, Smieszek A, Kucharczyk N, Bedford P.G.C, Marycz K. Intra-Vitreal Administration of Microvesicles Derived from Human Adipose-Derived Multipotent Stromal Cells Improves Retinal Functionality in Dogs with Retinal Degeneration.. J. Clin. Med. 2019;8:510.
    doi: 10.3390/jcm8040510pmc: PMC6518198pubmed: 31013950google scholar: lookup
  93. Cislo-Pakuluk A, Marycz K. A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications.. Stem Cell Rev. Rep. 2017;13:598–602.
    doi: 10.1007/s12015-017-9750-4pmc: PMC5602072pubmed: 28643176google scholar: lookup
  94. Kulig D, Zimoch-Korzycka A, Jarmoluk A, Marycz K. Study on Alginate–Chitosan Complex Formed with Different Polymers Ratio.. Polymers 2016;8:167.
    doi: 10.3390/polym8050167pmc: PMC6432350pubmed: 30979272google scholar: lookup

Citations

This article has been cited 5 times.
  1. Sarmiento Quintana D, Morales Fariña I, González Pérez J, Morales Doreste M, Jaber JR, Corbera JA. Prospective Comparative Study of Topical Tacrolimus and Sirolimus for the Treatment of Pigmentary Keratitis in Pug Dogs. Vet Sci 2026 Jan 5;13(1).
    doi: 10.3390/vetsci13010047pubmed: 41600703google scholar: lookup
  2. Meng L, Yang F, Cao Z, Wang C, Chen J, Zhu Y, Wang K, Liu J, Yan D, Pang Y. Wearing bacteriophages individually with an adhesive drug-loadable nanohelmet for treating ocular infections. Sci Adv 2025 Jul 11;11(28):eadx4183.
    doi: 10.1126/sciadv.adx4183pubmed: 40644532google scholar: lookup
  3. Huang Y, Tang H, Meng X, Zhao Z, Liu Y, Liu D, Chen B, Zou Z. Development of Large Hollow Particles for Pulmonary Delivery of Cyclosporine A. Pharmaceutics 2023 Aug 25;15(9).
    doi: 10.3390/pharmaceutics15092204pubmed: 37765173google scholar: lookup
  4. Ribeiro ACF, Esteso MA. Cyclodextrins as Drug Release Modulators and Toxic Compound Removal Agents. Biomolecules 2023 Jun 29;13(7).
    doi: 10.3390/biom13071056pubmed: 37509092google scholar: lookup
  5. Padjasek M, Cisło-Sankowska A, Lis-Bartos A, Qasem B, Marycz K. PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses. Int J Mol Sci 2023 Mar 17;24(6).
    doi: 10.3390/ijms24065735pubmed: 36982806google scholar: lookup
Subscribe to our newsletter
Join 99,579 horse owners like you who receive our email updates on horse health and nutrition.