ABSTRACT
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is an adaptive immune defence system that has gradually evolved in bacteria and archaea to combat invading viruses and exogenous DNA. Advances in technology have enabled researchers to enhance their understanding of the immune process in vivo and its potential for use in genome editing. Thus far, applications of CRISPR/Cas9 genome editing technology in ophthalmology have included gene therapy for corneal dystrophy, glaucoma, congenital cataract, Leber's congenital amaurosis, retinitis pigmentosa, Usher syndrome, fundus neovascular disease, proliferative vitreoretinopathy, retinoblastoma and other eye diseases. Additionally, the combination of CRISPR/Cas9 genome editing technology with adeno-associated virus vector and inducible pluripotent stem cells provides further therapeutic avenues for the treatment of eye diseases. Nonetheless, many challenges remain in the development of clinically feasible retinal genome editing therapy. This review discusses the development, as well as mechanism of CRISPR/Cas9 and its applications and challenges in gene therapy for eye diseases.
Subject(s)
CRISPR-Cas Systems , Retinitis Pigmentosa , Humans , Gene Editing , Genetic Therapy , Retinitis Pigmentosa/geneticsABSTRACT
The investigation aimed to evaluate the effects of Mcc950, an inhibitor of the NLRP3 inflammasome, on diabetic retinopathy (DR) mice. The general physiological condition of each group of mice was recorded. Retinal blood vessels were stained for observation of the density of blood vessels, and retinas were used for further morphological examination and fluorescent staining after the intravitreal injection of Mcc950. Mcc950 partially reversed hyperglycemia-induced vascular damage and had reduced histological changes compared to DR mice. IL-1ß production in mice retinas in the diabetic model (DM) group increased, but pretreatment with Mcc950 significantly reversed these changes. Additionally, Mcc950 engineered reduced FITC dextran extravasation and vascular leakage. Therefore, it played an apparent protective role in DR and could be a new treatment strategy for DR.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Diabetic Retinopathy/prevention & control , Furans/pharmacology , Indenes/pharmacology , Inflammasomes/antagonists & inhibitors , Inflammation Mediators/metabolism , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Retinal Neovascularization/prevention & control , Retinal Vessels/drug effects , Sulfonamides/pharmacology , Animals , Anti-Inflammatory Agents/administration & dosage , Blood Glucose/metabolism , Capillary Permeability/drug effects , Diabetic Retinopathy/immunology , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Disease Models, Animal , Disease Progression , Furans/administration & dosage , Indenes/administration & dosage , Inflammasomes/metabolism , Intravitreal Injections , Male , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Retinal Neovascularization/immunology , Retinal Neovascularization/metabolism , Retinal Neovascularization/pathology , Retinal Vessels/immunology , Retinal Vessels/metabolism , Retinal Vessels/pathology , Signal Transduction , Sulfonamides/administration & dosageABSTRACT
OBJECTIVE: To evaluate the efficacy of pars plana vitrectomy (PPV) combined with episcleral cryotherapy in treating vasoproliferative tumors of the retina (VPTR) with macular complications. METHODS: In this retrospective noncomparative interventional case-series analysis, we included 11 eyes of ten patients diagnosed with VPTR. All patients underwent comprehensive ophthalmic examinations and were treated with PPV combined with episcleral cryotherapy. Best-corrected visual acuity (BCVA), tumor activity, retinal morphological structure, and postoperative complications were evaluated. RESULTS: Macular complications included epimacular membrane (n = 10), macular hole (n = 3), and macular edema (n = 1). Tumors were treated with triple freeze-thaw episcleral cryotherapy during PPV. The mean logarithm of minimal angle of resolution (logMAR) BCVA dropped from 0.62 ± 0.58 to 0.39 ± 0.46. The difference between the mean values of logMAR BCVA before and after treatment was statistically significant (t = 2.48, P=0.033). The tumor activity was controlled effectively in nine cases. Compared with preoperative tumor activity, tumor activity after treatment was significantly lower (P < 0.01). The increase of central retinal thickness and the disruption of retinal layers were associated with macular holes, macular edema, and retinal proliferative membrane. After the treatment, visual acuity improved in 91% of the cases, and 73% had no long-term complications. CONCLUSION: PPV combined with episcleral cryotherapy promoted tumor regression, preserved retinal integrity, and improved visual acuity. Thus, the combination of PPV with episcleral cryotherapy can be considered effective and safe for the management of VPTR with macular complications.
