Retinal Development and Pathophysiology in Kcnj13 Knockout Mice

Purpose: We constructed and characterized knockout and conditional knockout mice for KCNJ13, encoding the inwardly rectifying K+ channel of the Kir superfamily Kir7.1, mutations in which cause both Snowflake Vitreoretinal Degeneration (SVD) and Retinitis pigmentosa (RP) to further elucidate the pathology of this disease and to develop a potential model system for gene therapy trials.Methods: A Kcnj13 knockout mouse line was constructed by inserting a gene trap cassette expressing beta-galactosidase flanked by FRT sites in intron 1 with LoxP sites flanking exon two and converted to a conditional knockout by FLP recombination followed by crossing with C57BL/6J mice having Cre driven by the VMD2 promoter. Lentiviral replacement of Kcnj13 was driven by the EF1a or VMD2 promoters.Results: Blue-Gal expression is evident in E12.5 brain ventricular choroid plexus, lens, neural retina layer, and anterior RPE. In the adult eye expression is seen in the ciliary body, RPE and choroid. Adult conditional Kcnj13 ko mice show loss of photoreceptors in the outer nuclear layer, inner nuclear layer thinning with loss of bipolar cells, and thinning and disruption of the outer plexiform layer, correlating with Cre expression in the overlying RPE which, although preserved, shows morphological disruption. Fundoscopy and OCT show signs of retinal degeneration consistent with the histology, and photopic and scotopic ERGs are decreased in amplitude or extinguished. Lentiviral based replacement of Kcnj13 resulted in increased ERG c- but not a- or b- wave amplitudes.Conclusion: Ocular KCNJ13 expression starts in the choroid, lens, ciliary body, and anterior retina, while later expression centers on the RPE with no/lower expression in the neuroretina. Although KCNJ13 expression is not required for survival of the RPE, it is necessary for RPE maintenance of the photoreceptors, and loss of the photoreceptor, outer plexiform, and outer nuclear layers occur in adult KCNJ13 cKO mice, concomitant with decreased amplitude and eventual extinguishing of the ERG and signs of retinitis pigmentosa on fundoscopy and OCT. Kcnj13 replacement resulting in recovery of the ERG c- but not a- and b-waves is consistent with the degree of photoreceptor degeneration seen on histology.

X-linked Retinoschisis Discovered after Congenital Cataract Surgery

X-linked retinoschisis (XLRS) is a rare, hereditary, and bilateral vitreoretinal degeneration, associating maculopathy and vitreoretinopathy. We report the case of X-linked retinoschisis diagnosed after congenital cataract surgery in a child.

Evaluation of hyaloid–retinal relationship during triamcinolone-assisted vitrectomy for primary rhegmatogenous retinal detachment

Aims: To determine hyaloid–retinal relationship in primary rhegmatogenous retinal detachment during vitreous surgery. Methods: This is a prospective, interventional study of patients (n = 72) undergoing triamcinolone-assisted 25G vitreous surgery for primary rhegmatogenous retinal detachment. Hyaloid–retinal relationship was noted intraoperatively to identify regions and patterns of firm attachment and was classified into subgroups. Analysis was done to determine association between hyaloid–retinal relationship patterns and preoperative findings: posterior vitreous detachment, proliferative vitreoretinopathy, type of retinal tear, the presence of peripheral degenerations, and postoperative outcomes. Results: Three patterns of hyaloid–retinal relationship were identified: type1 (complete absence of posterior vitreous detachment (21%)), type 2 (incomplete posterior vitreous detachment (47%)) and type 3 (complete posterior vitreous detachment (32%)). Posterior vitreous detachment in some form was present in 84% of the cases with retinal tears as the causative break but none of the cases with retinal holes (p < 0.001). None of the cases with vitreoretinal degeneration had complete posterior vitreous detachment (p = 0.001). 69% of proliferative vitreoretinopathy–C cases had type 1 hyaloid–retinal relationship as compared to 11% cases with no proliferative vitreoretinopathy (p < 0.001). Proliferative vitreoretinopathy-related anatomical failure was seen in 7.5%, and 80% of these eyes with recurrent RD had type 1 hyaloid–retinal relationship (p<0.001). Nearly half the patients diagnosed as complete posterior vitreous detachment preoperatively were found to have incomplete posterior vitreous detachment intraoperatively. Conclusions: Majority of the cases with rhegmatogenous retinal detachment have some form of strong vitreoretinal adhesion. Hyaloid–retinal relationship varies with types of retinal breaks, retinal degeneration, and proliferative vitreoretinopathy. Intraoperative hyaloid–retinal relationship is frequently different from that assessed before surgery and the proposed classification may improve surgical decision making and prognostication.

Stickler Syndrome Type 1 with Short Stature and Atypical Ocular Manifestations

Stickler syndrome or hereditary progressive arthroophthalmopathy is a heterogeneous group of collagen tissue disorders, characterized by orofacial features, ophthalmological features (high myopia, vitreoretinal degeneration, retinal detachment, and presenile cataracts), hearing impairment, mild spondyloepiphyseal dysplasia, and/or early onset arthritis. Stickler syndrome type I (ocular form) is caused by mutation in the COL2A1 gene. Ptosis and uveitis are relatively rare ophthalmological manifestations of this syndrome. We report an Indian boy having 2710C>T mutation in COL2A1 gene demonstrating short stature, ptosis, and uveitis with Stickler syndrome.