FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Mol Ther Methods Clin Dev / Ocular toxicity, distribution, and shedding of intravitreal ...
Molecular therapy. Methods & clinical development2024; 32(4); 101360; doi: 10.1016/j.omtm.2024.101360

Ocular toxicity, distribution, and shedding of intravitreal AAV-eqIL-10 in horses.

Abstract: Non-infectious uveitis (NIU) is a painful recurrent disease affecting 2%-5% of horses. Current treatments require frequent administration with associated adverse events. In a previous study, intravitreal (IVT) adeno-associated virus (AAV) harboring equine interleukin-10 (eqIL-10) cDNA inhibited experimental uveitis in rats. The goal of this study was to evaluate the ocular tolerability, vector genome (vg) distribution, and vector shedding following an IVT injection of AAV8-eqIL-10 in normal horses with the hypothesis that it would be well tolerated in a dose-dependent manner in horses. Injections were well tolerated with mild transient signs of ocular inflammation; however, horses receiving the highest dose developed keratic precipitates. The vgs were not detected in the tears 3 days after injection, or in urine or feces at any time. Aqueous and vitreous humor eqIL-10 levels increased to higher than 1.5 ng/mL, more than 20 times higher than reported effective endogenous and induced levels. The vgs were detected in ocular tissues, and systemic distribution was identified only in the liver and kidney. No systemic effects were identified 86 days after dosing with IVT AAV-eqIL-10. Further investigation of lower doses of IVT AAV8-eqIL-10 therapy is an important next step toward a safe and effective single-dose treatment of equine uveitis with broader implications for treating NIU in humans.
© 2024 The Author(s).
Get Full Text
Publication Date: 2024-10-28 PubMed ID: 39703903PubMed Central: PMC11656199DOI: 10.1016/j.omtm.2024.101360Google 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

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.

Overview

  • This study investigates the safety, distribution, and shedding of an experimental gene therapy using AAV-eqIL-10 injected directly into the eyes of healthy horses to treat non-infectious uveitis (NIU), a recurrent eye disease.
  • The research aims to determine if this treatment is well tolerated and how the viral vector spreads and persists in the body after administration.

Background

  • Non-infectious uveitis (NIU) is a painful and recurrent inflammatory eye condition affecting 2%-5% of horses, which causes discomfort and vision issues.
  • Existing treatments need frequent administration and are associated with potential adverse effects.
  • Prior research showed that delivering the gene for equine interleukin-10 (eqIL-10), an anti-inflammatory cytokine, via adeno-associated virus (AAV) vectors into the eye suppressed experimental uveitis in rats.
  • This suggested potential for gene therapy as a single-dose treatment that could provide sustained anti-inflammatory effects.

Study Objective

  • The primary goal was to evaluate ocular safety (toxicity), the biodistribution of the viral vector genomes (vgs), and shedding of the vector following a single intravitreal (IVT) injection of AAV8-eqIL-10 into the eyes of normal horses.
  • The hypothesis was that the treatment would be tolerated in a dose-dependent manner—that is, higher doses could cause more side effects but still be safe.

Methods

  • Healthy horses were administered varying doses of AAV8-eqIL-10 directly into the eye’s vitreous humor via intravitreal injection.
  • Ocular inflammation and other signs of toxicity were monitored to assess tolerability.
  • Tears, urine, feces, and ocular tissues were sampled to detect presence and shedding of viral vector genomes over time.
  • Levels of eqIL-10 protein were measured in ocular fluids (aqueous and vitreous humor) to evaluate the biological activity of the gene therapy.
  • Systemic organs such as liver and kidney were analyzed to assess distribution beyond the eye.
  • Long-term effects were monitored up to 86 days post-injection.

Key Findings

  • Tolerability: The injections were generally well tolerated. Mild and transient ocular inflammation was observed, indicating some eye irritation but no severe adverse effects.
  • High Dose Effects: Horses receiving the highest dose developed keratic precipitates—accumulations of inflammatory cells on the corneal endothelium, suggesting a localized immune response at high dosage levels.
  • Vector Shedding: Vector genomes were undetectable in tears after 3 days and were not found in urine or feces at any time point, suggesting minimal risk of environmental shedding or spread via bodily excretions.
  • Protein Expression: Levels of eqIL-10 in eye fluids rose to over 1.5 ng/mL, which is more than 20 times greater than levels previously known to be effective, indicating successful gene delivery and protein expression.
  • Biodistribution: Viral genomes were detected in ocular tissues, confirming localized vector presence.
  • Systemic Distribution: Aside from the eye, vector genomes were found only in the liver and kidney, likely due to natural systemic circulation and clearance processes.
  • Safety: No systemic adverse effects were observed 86 days post-treatment, supporting the overall safety of the approach in this timeframe.

Implications and Future Directions

  • The study supports that single-dose intravitreal injection of AAV8-eqIL-10 is a promising therapeutic strategy to deliver anti-inflammatory treatment for equine uveitis.
  • Since the therapy achieved high intraocular levels of eqIL-10 with minimal systemic distribution and manageable side effects, it could reduce or replace the need for frequent conventional treatments.
  • Finding the optimal lower dose that balances efficacy and safety is important for future research.
  • The successful demonstration in horses could have broader implications for treating non-infectious uveitis in humans, as horses are often good models for human ocular diseases.
  • Further studies would be needed to evaluate long-term safety, efficacy in diseased eyes, and possible immune responses over extended periods.

Cite This Article

APA
Young K, Hasegawa T, Vridhachalam N, Henderson N, Salmon JH, McCall TF, Hirsch ML, Gilger BC. (2024). Ocular toxicity, distribution, and shedding of intravitreal AAV-eqIL-10 in horses. Mol Ther Methods Clin Dev, 32(4), 101360. https://doi.org/10.1016/j.omtm.2024.101360

Publication

Molecular therapy. Methods & clinical development
ISSN: 2329-0501
NlmUniqueID: 101624857
Country: United States
Language: English
Volume: 32
Issue: 4
Pages: 101360
PII: 101360

Researcher Affiliations

Young, Kim
  • Clinical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
Hasegawa, Tomoko
  • Ophthalmology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Vridhachalam, Naveen
  • Ophthalmology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Henderson, Nichol
  • Clinical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
Salmon, Jacklyn H
  • Clinical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
McCall, Trace F
  • Ophthalmology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Hirsch, Matthew L
  • Ophthalmology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Gilger, Brian C
  • Clinical Sciences, North Carolina State University, Raleigh, NC 27607, USA.

Conflict of Interest Statement

B.C.G. and M.L.H. hold a provisional patent for the clinical therapeutic investigated.

References

This article includes 58 references
  1. Jones NP. The Manchester Uveitis Clinic: The First 3000 Patients-Epidemiology and Casemix. Ocul. Immunol. Inflamm. 2015;23:118–126.
    doi: 10.3109/09273948.2013.855799pubmed: 24295124google scholar: lookup
  2. Thorne JE, Suhler E, Skup M, Tari S, Macaulay D, Chao J, Ganguli A. Prevalence of Noninfectious Uveitis in the United States: A Claims-Based Analysis. JAMA Ophthalmol. 2016;134:1237–1245.
    doi: 10.1001/jamaophthalmol.2016.3229pubmed: 27608193google scholar: lookup
  3. Abdulaal MR, Abiad BH, Hamam RN. Uveitis in the Aging Eye: Incidence, Patterns, and Differential Diagnosis. J. Ophthalmol. 2015;2015.
    doi: 10.1155/2015/509456pmc: PMC4452188pubmed: 26090218google scholar: lookup
  4. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California: The Northern California Epidemiology of Uveitis Study. Ophthalmology 2004;111:491–500.
    doi: 10.1016/j.ophtha.2003.06.014pubmed: 15019324google scholar: lookup
  5. Gerding JC, Gilger BC. Prognosis and impact of equine recurrent uveitis. Equine Vet. J. 2016;48:290–298.
    doi: 10.1111/evj.12451pubmed: 25891653google scholar: lookup
  6. Deeg CA, Hauck SM, Amann B, Pompetzki D, Altmann F, Raith A, Schmalzl T, Stangassinger M, Ueffing M. Equine Recurrent Uveitis – A Spontaneous Horse Model of Uveitis. Ophthalmic Res. 2008;40:151–153.
    doi: 10.1159/000119867pubmed: 18421230google scholar: lookup
  7. Witkowski L, Cywinska A, Paschalis-Trela K, Crisman M, Kita J. Multiple etiologies of equine recurrent uveitis – A natural model for human autoimmune uveitis: A brief review. Comp. Immunol. Microbiol. Infect. Dis. 2016;44:14–20.
    doi: 10.1016/j.cimid.2015.11.004pubmed: 26851589google scholar: lookup
  8. 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
  9. Willermain F, Rosenbaum JT, Bodaghi B, Rosenzweig HL, Childers S, Behrend T, Wildner G, Dick AD. Interplay between innate and adaptive immunity in the development of non-infectious uveitis. Prog. Retin. Eye Res. 2012;31:182–194.
    doi: 10.1016/j.preteyeres.2011.11.004pmc: PMC3288447pubmed: 22120610google scholar: lookup
  10. Srivastava A, Rajappa M, Kaur J. Uveitis: Mechanisms and recent advances in therapy. Clin. Chim. Acta. 2010;411:1165–1171.
    doi: 10.1016/j.cca.2010.04.017pubmed: 20416287google scholar: lookup
  11. Jones NP. The Manchester Uveitis Clinic: the first 3000 patients, 2: uveitis manifestations, complications, medical and surgical management. Ocul. Immunol. Inflamm. 2015;23:127–134.
    pubmed: 25393634
  12. Bastola P, Song L, Gilger BC, Hirsch ML. Adeno-Associated Virus Mediated Gene Therapy for Corneal Diseases. Pharmaceutics 2020;12:767.
    doi: 10.3390/pharmaceutics12080767pmc: PMC7464341pubmed: 32823625google scholar: lookup
  13. Miraldi Utz V, Coussa RG, Antaki F, Traboulsi EI. Gene therapy for RPE65-related retinal disease: Ophthalmic Genetics. Ophthalmic Genet. 2018;39:671–677.
    doi: 10.1080/13816810.2018.1533027pubmed: 30335549google scholar: lookup
  14. Patel U, Boucher M, de Léséleuc L, Visintini S. Voretigene Neparvovec: An Emerging Gene Therapy for the Treatment of Inherited Blindness. .
    pubmed: 30855774
  15. Li C, Samulski RJ. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 2020;21:255–272.
    doi: 10.1038/s41576-019-0205-4pubmed: 32042148google scholar: lookup
  16. Tsai M.-L., Horng C.-T., Chen S.-L., Xiao X., Wang C.-H., Tsao Y.-P. Suppression of experimental uveitis by a recombinant adeno-associated virus vector encoding interleukin-1 receptor antagonist. Mol. Vis. 2009;15:1542–1552.
    pmc: PMC2723168pubmed: 19693263
  17. Chan Y.K., Dick A.D., Hall S.M., Langmann T., Scribner C.L., Mansfield B.C., Ocular Gene Therapy Inflammation Working Group Inflammation in Viral Vector-Mediated Ocular Gene Therapy: A Review and Report From a Workshop Hosted by the Foundation Fighting Blindness, 9/2020. Transl. Vis. Sci. Technol. 2021;10 doi: 10.1167/tvst.10.4.3.
    doi: 10.1167/tvst.10.4.3pmc: PMC8024774pubmed: 34003982google scholar: lookup
  18. Bogner B., Boye S.L., Min S.H., Peterson J.J., Ruan Q., Zhang Z., Reitsamer H.A., Hauswirth W.W., Boye S.E. Capsid Mutated Adeno-Associated Virus Delivered to the Anterior Chamber Results in Efficient Transduction of Trabecular Meshwork in Mouse and Rat. PLoS One. 2015;10 doi: 10.1371/journal.pone.0128759.
    doi: 10.1371/journal.pone.0128759pmc: PMC4460001pubmed: 26052939google scholar: lookup
  19. Song L., Llanga T., Conatser L.M., Zaric V., Gilger B.C., Hirsch M.L. Serotype survey of AAV gene delivery via subconjunctival injection in mice. Gene Ther. 2018;25:402–414. doi: 10.1038/s41434-018-0035-6.
    doi: 10.1038/s41434-018-0035-6pmc: PMC11610513pubmed: 30072815google scholar: lookup
  20. Buie L.K., Rasmussen C.A., Porterfield E.C., Ramgolam V.S., Choi V.W., Markovic-Plese S., Samulski R.J., Kaufman P.L., Borrás T. Self-complementary AAV Virus (scAAV) Safe and Long-term Gene Transfer in the Trabecular Meshwork of Living Rats and Monkeys. Invest. Ophthalmol. Vis. Sci. 2010;51:236–248. doi: 10.1167/iovs.09-3847.
    doi: 10.1167/iovs.09-3847pmc: PMC2869048pubmed: 19684004google scholar: lookup
  21. Moore K.W., de Waal Malefyt R., Coffman R.L., O’Garra A. Interleukin-10 and the Interleukin-10 Receptor. Annu. Rev. Immunol. 2001;19:683–765. doi: 10.1146/annurev.immunol.19.1.683.
    doi: 10.1146/annurev.immunol.19.1.683pubmed: 11244051google scholar: lookup
  22. Iyer S.S., Cheng G. Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease. Crit. Rev. Immunol. 2012;32:23–63.
    pmc: PMC3410706pubmed: 22428854
  23. Couper K.N., Blount D.G., Riley E.M. IL-10: The Master Regulator of Immunity to Infection. J. Immunol. 2008;180:5771–5777. doi: 10.4049/jimmunol.180.9.5771.
    doi: 10.4049/jimmunol.180.9.5771pubmed: 18424693google scholar: lookup
  24. O’Garra A., Barrat F.J., Castro A.G., Vicari A., Hawrylowicz C. Strategies for use of IL-10 or its antagonists in human disease. Immunol. Rev. 2008;223:114–131. doi: 10.1111/j.1600-065X.2008.00635.x.
    doi: 10.1111/j.1600-065X.2008.00635.xpubmed: 18613832google scholar: lookup
  25. Trittibach P., Barker S.E., Broderick C.A., Natkunarajah M., Duran Y., Robbie S.J., Bainbridge J.W.B., Smith A.J., Sarra G.-M., Dick A.D., Ali R.R. Lentiviral-Vector Mediated Expression of Murine IL-1 Receptor Antagonist or IL-10 Reduces the Severity of Endotoxin-Induced Uveitis. Gene Ther. 2008;15:1478–1488. doi: 10.1038/gt.2008.109.
    doi: 10.1038/gt.2008.109pmc: PMC2816393pubmed: 18580969google scholar: lookup
  26. Broderick C.A., Smith A.J., Balaggan K.S., Georgiadis A., Buch P.K., Trittibach P.C., Barker S.E., Sarra G.-M., Thrasher A.J., Dick A.D., Ali R.R. Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis. Mol. Ther. 2005;12:369–373.
    pubmed: 16043105
  27. Ghasemi H., Ghazanfari T., Yaraee R., Owlia P., Hassan Z.M., Faghihzadeh S. Roles of IL-10 in ocular inflammations: a review. Ocul. Immunol. Inflamm. 2012;20:406–418.
    pubmed: 23163602
  28. Crabtree E., Uribe K., Smith S.M., Roberts D., Salmon J.H., Bower J.J., Song L., Bastola P., Hirsch M.L., Gilger B.C. Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy. PLoS One. 2022;17 doi: 10.1371/journal.pone.0270972.
    doi: 10.1371/journal.pone.0270972pmc: PMC9387812pubmed: 35980983google scholar: lookup
  29. Crabtree E., Song L., Llanga T., Bower J.J., Cullen M., Salmon J.H., Hirsch M.L., Gilger B.C. AAV-mediated expression of HLA-G1/5 reduces severity of experimental autoimmune uveitis. Sci. Rep. 2019;9 doi: 10.1038/s41598-019-56462-3.
    doi: 10.1038/s41598-019-56462-3pmc: PMC6934797pubmed: 31882729google scholar: lookup
  30. Patipa L.A., Sherlock C.E., Witte S.H., Pirie G.D., Berghaus R.D., Peroni J.F. Risk factors for colic in equids hospitalized for ocular disease. J. Am. Vet. Med. Assoc. 2012;240:1488–1493.
    pubmed: 22657933
  31. Scherrer N.M., Lassaline M., Richardson D.W., Stefanovski D. Interval prevalence of and factors associated with colic in horses hospitalized for ocular or orthopedic disease. J. Am. Vet. Med. Assoc. 2016;249:90–95.
    pubmed: 27308887
  32. Curto E.M., Griffith E.H., Posner L.P., Walsh K.T., Balko J.A., Gilger B.C. Factors associated with postoperative complications in healthy horses after general anesthesia for ophthalmic versus non-ophthalmic procedures: 556 cases (2012–2014) J. Am. Vet. Med. Assoc. 2018;252:1113–1119.
    pubmed: 29641332
  33. Beebe A.M., Cua D.J., de Waal Malefyt R. The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS) Cytokine Growth Factor Rev. 2002;13:403–412. doi: 10.1016/S1359-6101(02)00025-4.
    doi: 10.1016/S1359-6101(02)00025-4pubmed: 12220553google scholar: lookup
  34. Li R., Zhang L., Peng C., Lu Y., Liu Z., Xu X., Wang C., Hu R., Tan W., Zhou L., et al. Chronic Expression of Interleukin-10 Transgene Modulates Cardiac Sympathetic Ganglion Resulting in Reduced Ventricular Arrhythmia. Hum. Gene Ther. 2024;35:114–122. doi: 10.1089/hum.2023.160.
    doi: 10.1089/hum.2023.160pubmed: 38131291google scholar: lookup
  35. Moss K.L., Jiang Z., Dodson M.E., Linardi R.L., Haughan J., Gale A.L., Grzybowski C., Engiles J.E., Stefanovski D., Robinson M.A., Ortved K.F. Sustained Interleukin-10 Transgene Expression Following Intra-Articular AAV5-IL-10 Administration to Horses. Hum. Gene Ther. 2020;31:110–118. doi: 10.1089/hum.2019.195.
    doi: 10.1089/hum.2019.195pmc: PMC7872004pubmed: 31773987google scholar: lookup
  36. Li C., Samulski R.J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 2020;21:255–272.
    pubmed: 32042148
  37. Xiong W., Wu D.M., Xue Y., Wang S.K., Chung M.J., Ji X., Rana P., Zhao S.R., Mai S., Cepko C.L. AAV cis-regulatory sequences are correlated with ocular toxicity. Proc. Natl. Acad. Sci. USA. 2019;116:5785–5794.
    pmc: PMC6431174pubmed: 30833387
  38. Mehta N., Robbins D.A., Yiu G. Ocular inflammation and treatment emergent adverse events in retinal gene therapy. Int. Ophthalmol. Clin. 2021;61:151–177.
    pmc: PMC8259781pubmed: 34196322
  39. Katada Y., Kobayashi K., Tsubota K., Kurihara T. Evaluation of AAV-DJ vector for retinal gene therapy. PeerJ. 2019;7
    pmc: PMC6339780pubmed: 30671314
  40. Conti P., Kempuraj D., Kandere K., Di Gioacchino M., Barbacane R.C., Castellani M.L., Felaco M., Boucher W., Letourneau R., Theoharides T.C. IL-10, an inflammatory/inhibitory cytokine, but not always. Immunol. Lett. 2003;86:123–129.
    pubmed: 12644313
  41. Wilson E.B., Brooks D.G. Negative Co-Receptors and Ligands; 2011. The Role of IL-10 in Regulating Immunity to Persistent Viral Infections; pp. 39–65.
    pmc: PMC3492216pubmed: 20703965
  42. Abu El-Asrar A.M., Mohammad G., Nawaz M.I., Siddiquei M.M., Van Den Eynde K., Mousa A., De Hertogh G., Opdenakker G. Relationship between Vitreous Levels of Matrix Metalloproteinases and Vascular Endothelial Growth Factor in Proliferative Diabetic Retinopathy. PLoS One. 2013;8 doi: 10.1371/journal.pone.0085857.
    doi: 10.1371/journal.pone.0085857pmc: PMC3877391pubmed: 24392031google scholar: lookup
  43. Curto E., Messenger K.M., Salmon J.H., Gilger B.C. Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis. Vet. Immunol. Immunopathol. 2016;182:43–51. doi: 10.1016/j.vetimm.2016.09.008.
    doi: 10.1016/j.vetimm.2016.09.008pubmed: 27863549google scholar: lookup
  44. Wang Y., Yu P., Li Y., Zhao Z., Wu X., Zhang L., Feng J., Hong J.-S. Early-Released Interleukin-10 Significantly Inhibits Lipopolysaccharide-Elicited Neuroinflammation In Vitro. Cells. 2021;10:2173. doi: 10.3390/cells10092173.
    doi: 10.3390/cells10092173pmc: PMC8466025pubmed: 34571824google scholar: lookup
  45. Fang I.-M., Lin C.-P., Yang C.-H., Chiang B.-L., Yang C.-M., Chau L.-Y., Chen M.-S. Inhibition of experimental autoimmune anterior uveitis by adenovirus-mediated transfer of the interleukin-10 gene. J. Ocul. Pharmacol. Therapeut. 2005;21:420–428.
    pubmed: 16386083
  46. Huynh T., Reed C., Blackwell Z., Phelps P., Herrera L.C.P., Almodovar J., Zaharoff D.A., Wolchok J. Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury. Sci. Rep. 2023;13:1983. doi: 10.1038/s41598-023-27981-x.
    doi: 10.1038/s41598-023-27981-xpmc: PMC9898301pubmed: 36737628google scholar: lookup
  47. Hussey G.S., Goehring L.S., Lunn D.P., Hussey S.B., Huang T., Osterrieder N., Powell C., Hand J., Holz C., Slater J. Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions. Vet. Res. 2013;44:118. doi: 10.1186/1297-9716-44-118.
    doi: 10.1186/1297-9716-44-118pmc: PMC4028784pubmed: 24308772google scholar: lookup
  48. Guo Y., Chen J., Ji W., Xu L., Xie Y., He S., Lai C., Hou K., Li Z., Chen G., Wu Z. High-titer AAV disrupts cerebrovascular integrity and induces lymphocyte infiltration in adult mouse brain. Mol. Ther. Methods Clin. Dev. 2023;31 doi: 10.1016/j.omtm.2023.08.021.
    doi: 10.1016/j.omtm.2023.08.021pmc: PMC10518493pubmed: 37753218google scholar: lookup
  49. Ghoraba H.H., Akhavanrezayat A., Karaca I., Yavari N., Lajevardi S., Hwang J., Regenold J., Matsumiya W., Pham B., Zaidi M., et al. Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses. Clin. Ophthalmol. 2022;16:1753–1771. doi: 10.2147/OPTH.S364200.
    doi: 10.2147/OPTH.S364200pmc: PMC9173725pubmed: 35685379google scholar: lookup
  50. Reichel F.F., Peters T., Wilhelm B., Biel M., Ueffing M., Wissinger B., Bartz-Schmidt K.U., Klein R., Michalakis S., Fischer M.D., RD-CURE Consortium Humoral Immune Response After Intravitreal But Not After Subretinal AAV8 in Primates and Patients. Invest. Ophthalmol. Vis. Sci. 2018;59:1910–1915. doi: 10.1167/iovs.17-22494.
    doi: 10.1167/iovs.17-22494pubmed: 29677353google scholar: lookup
  51. WB B.J., Mehat M.S., Venki S., Robbie S.J., Barker S.E., Caterina R., Anastasios G., Mowat F.M., Beattie S.G., Gardner P.J., et al. Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis. N. Engl. J. Med. 2015;372:1887–1897. doi: 10.1056/NEJMoa1414221.
    doi: 10.1056/NEJMoa1414221pmc: PMC4497809pubmed: 25938638google scholar: lookup
  52. Reichel F.F., Dauletbekov D.L., Klein R., Peters T., Ochakovski G.A., Seitz I.P., Wilhelm B., Ueffing M., Biel M., Wissinger B., et al. AAV8 Can Induce Innate and Adaptive Immune Response in the Primate Eye. Mol. Ther. 2017;25:2648–2660. doi: 10.1016/j.ymthe.2017.08.018.
    doi: 10.1016/j.ymthe.2017.08.018pmc: PMC5768589pubmed: 28970046google scholar: lookup
  53. Bouquet C., Vignal Clermont C., Galy A., Fitoussi S., Blouin L., Munk M.R., Valero S., Meunier S., Katz B., Sahel J.A., Thomasson N. Immune Response and Intraocular Inflammation in Patients With Leber Hereditary Optic Neuropathy Treated With Intravitreal Injection of Recombinant Adeno-Associated Virus 2 Carrying the ND4 Gene: A Secondary Analysis of a Phase 1/2 Clinical Trial. JAMA Ophthalmol. 2019;137:399–406. doi: 10.1001/jamaophthalmol.2018.6902.
    doi: 10.1001/jamaophthalmol.2018.6902pmc: PMC6459107pubmed: 30730541google scholar: lookup
  54. Cukras C., Wiley H.E., Jeffrey B.G., Sen H.N., Turriff A., Zeng Y., Vijayasarathy C., Marangoni D., Ziccardi L., Kjellstrom S., et al. Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a Phase I/IIa Trial by Intravitreal Delivery. Mol. Ther. 2018;26:2282–2294. doi: 10.1016/j.ymthe.2018.05.025.
    doi: 10.1016/j.ymthe.2018.05.025pmc: PMC6127971pubmed: 30196853google scholar: lookup
  55. Seitz I.P., Michalakis S., Wilhelm B., Reichel F.F., Ochakovski G.A., Zrenner E., Ueffing M., Biel M., Wissinger B., Bartz-Schmidt K.U., et al. Superior Retinal Gene Transfer and Biodistribution Profile of Subretinal Versus Intravitreal Delivery of AAV8 in Nonhuman Primates. Invest. Ophthalmol. Vis. Sci. 2017;58:5792–5801. doi: 10.1167/iovs.17-22473.
    doi: 10.1167/iovs.17-22473pubmed: 29117317google scholar: lookup
  56. Aurnhammer C., Haase M., Muether N., Hausl M., Rauschhuber C., Huber I., Nitschko H., Busch U., Sing A., Ehrhardt A., Baiker A. Universal real-time PCR for the detection and quantification of adeno-associated virus serotype 2-derived inverted terminal repeat sequences. Hum. Gene Ther. Methods. 2012;23:18–28. doi: 10.1089/hgtb.2011.034.
    doi: 10.1089/hgtb.2011.034pubmed: 22428977google scholar: lookup
  57. Eaton J.S., Miller P.E., Bentley E., Thomasy S.M., Murphy C.J. The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology. J. Ocul. Pharmacol. Therapeut. 2017;33:718–734. doi: 10.1089/jop.2017.0108.
    doi: 10.1089/jop.2017.0108pubmed: 29239680google scholar: lookup
  58. Zhang X., Anthony B., Chai Z., Lee Dobbins A., Sutton R.B., Li C. Membrane fusion FerA domains enhance adeno-associated virus vector transduction. Biomaterials. 2020;241 doi: 10.1016/j.biomaterials.2020.119906.
    doi: 10.1016/j.biomaterials.2020.119906pmc: PMC7080211pubmed: 32114218google scholar: lookup

Citations

This article has been cited 1 times.
  1. Young KAS, Schnabel LV, Gilger BC. Cell and Gene Therapy in Equine Ocular Disease.. Vet Ophthalmol 2026 Mar;29(2):e70151.
    doi: 10.1111/vop.70151pubmed: 41623202google scholar: lookup
Subscribe to our newsletter
Join 99,001 horse owners like you who receive our email updates on horse health and nutrition.