Dataset Information

Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.

ABSTRACT:

Purpose

Spectral-domain optical coherence tomography (SD-OCT) was used to characterize the retinal phenotype, natural history, and treatment responses in a mouse model of X-linked retinoschisis (Rs1-KO) and to identify new structural markers of AAV8-mediated gene therapy outcome.

Methods

Optical coherence tomography scans were performed on wild-type and Rs1-KO mouse retinas between 1 and 12 months of age and on Rs1-KO mice after intravitreal injection of AAV8-scRS/IRBPhRS (AAV8-RS1). Cavities and photoreceptor outer nuclear layer (ONL) thickness were measured, and outer retina reflective band (ORRB) morphology was examined with age and after AAV8-RS1 treatment. Outer retina reflective band morphology was compared to immunohistochemical staining of the outer limiting membrane (OLM) and photoreceptor inner segment (IS) mitochondria and to electron microscopy (EM) images of IS.

Results

Retinal cavity size in Rs1-KO mice increased between 1 and 4 months and decreased thereafter, while ONL thickness declined steadily, comparable to previous histologic studies. Wild-type retina had four ORRBs. In Rs1-KO, ORRB1was fragmented from 1 month, but was normal after 8 months; ORRB2 and ORRB3 were merged at all ages. Outer retina reflective band morphology returned to normal after AAV-RS1 therapy, paralleling the recovery of the OLM and IS mitochondria as indicated by anti-?-catenin and anti-COX4 labeling, respectively, and EM.

Conclusions

Spectral-domain OCT is a sensitive, noninvasive tool to monitor subtle changes in retinal morphology, disease progression, and effects of therapies in mouse models. The ORRBs may be useful to assess the outcome of gene therapy in the treatment of X-linked retinoschisis patients.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC4968785 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.

Zeng Yong Y Petralia Ronald S RS Vijayasarathy Camasamudram C Wu Zhijian Z Hiriyanna Suja S Song Hongman H Wang Ya-Xian YX Sieving Paul A PA Bush Ronald A RA

Investigative ophthalmology & visual science 20160701 9

<h4>Purpose</h4>Spectral-domain optical coherence tomography (SD-OCT) was used to characterize the retinal phenotype, natural history, and treatment responses in a mouse model of X-linked retinoschisis (Rs1-KO) and to identify new structural markers of AAV8-mediated gene therapy outcome.<h4>Methods</h4>Optical coherence tomography scans were performed on wild-type and Rs1-KO mouse retinas between 1 and 12 months of age and on Rs1-KO mice after intravitreal injection of AAV8-scRS/IRBPhRS (AAV8-RS ...[more]

PMID: 27409484

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Project description:To describe the spectral-domain optical coherence tomography (SD OCT) features of peripheral retinal findings using an ultra-widefield (UWF) steering technique to image the retinal periphery.Observational study.A total of 68 patients (68 eyes) with 19 peripheral retinal features.Spectral-domain OCT-based structural features.Nineteen peripheral retinal features, including vortex vein, congenital hypertrophy of the retinal pigment epithelium, pars plana, ora serrata pearl, typical cystoid degeneration (TCD), cystic retinal tuft, meridional fold, lattice and cobblestone degeneration, retinal hole, retinal tear, rhegmatogenous retinal detachment, typical degenerative senile retinoschisis, peripheral laser coagulation scars, ora tooth, cryopexy scars (retinal tear and treated retinoblastoma scar), bone spicules, white without pressure, and peripheral drusen, were identified by peripheral clinical examination. Near-infrared scanning laser ophthalmoscopy images and SD OCT of these entities were registered to UWF color photographs.Spectral-domain OCT resolved structural features of all peripheral findings. Dilated hyporeflective tubular structures within the choroid were observed in the vortex vein. Loss of retinal lamination, neural retinal attenuation, retinal pigment epithelium loss, or hypertrophy was seen in several entities, including congenital hypertrophy of the retinal pigment epithelium, ora serrata pearl, TCD, cystic retinal tuft, meridional fold, lattice, and cobblestone degenerations. Hyporeflective intraretinal spaces, indicating cystoid or schitic fluid, were seen in ora serrata pearl, ora tooth, TCD, cystic retinal tuft, meridional fold, retinal hole, and typical degenerative senile retinoschisis. The vitreoretinal interface, which often consisted of lamellae-like structures of the condensed cortical vitreous near or adherent to the neural retina, appeared clearly in most peripheral findings, confirming its association with many low-risk and vision-threatening pathologies, such as lattice degeneration, meridional folds, retinal breaks, and rhegmatogenous retinal detachments.Ultra-widefield steering-based SD OCT imaging of the retinal periphery is feasible with current commercially available devices and provides detailed anatomic information of the peripheral retina, including benign and pathologic entities, not previously imaged. This imaging technique may deepen our structural understanding of these entities and their potentially associated macular and systemic pathologies, and may influence decision-making in clinical practice, particularly in areas with teleretinal capabilities but poor access to retinal specialists.

Dataset Information

Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.

Purpose

Methods

Results

Conclusions

Publications

Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.

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