Dataset Information

A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis.

ABSTRACT:

Purpose

Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis.

Methods

We identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, and monitored disease progression over 14 months by fundus photography, fluorescein angiography, and optical coherence tomography (OCT). After necropsy, we evaluated anatomic and cellular changes by immunohistochemistry and transcriptomic changes using single-nuclei RNA-sequencing (snRNA-seq). Finally, we performed Sanger and whole exome sequencing with focus on the RS1 gene.

Results

Affected eyes demonstrated posterior hyaloid traction and progressive splitting of the outer plexiform layer on OCT. Immunohistochemistry showed increased GFAP expression in Müller glia and loss of ramified Iba-1+ microglia, suggesting macro- and microglial activation with minimal photoreceptor alterations. SnRNA-seq revealed gene expression changes predominantly in cones and retinal ganglion cells involving chromatin modification, suggestive of cellular stress at the fovea. No defects in the RS1 gene or its expression were detected.

Conclusions

This nonhuman primate model of foveoschisis reveals insights into how acquired myopic traction leads to phenotypically similar morphologic and cellular changes as congenital XLRS without alterations in RS1.

SUBMITTER: Sin TN

PROVIDER: S-EPMC9896856 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis.

Sin Tzu-Ni TN Kim Sangbae S Li Yumei Y Wang Jun J Chen Rui R Chung Sook Hyun SH Kim Soohyun S Casanova M Isabel MI Park Sangwan S Smit-McBride Zeljka Z Sun Ning N Pomerantz Ori O Roberts Jeffrey A JA Guan Bin B Hufnagel Robert B RB Moshiri Ala A Thomasy Sara M SM Sieving Paul A PA Yiu Glenn G

Investigative ophthalmology & visual science 20230101 1

<h4>Purpose</h4>Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multim ...[more]

PMID: 36689233

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Project description:Purpose: To evaluate the short- and long-term effect of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling on visual acuity and macular morphology in myopic foveoschisis (MF) patients and to identify potential prognostic factors. Methods: We retrospectively analyzed the clinical data of patients with MF who underwent PPV with ILM peeling by the same senior fundus surgeon at Beijing Friendship Hospital from January 2016 to December 2022. The peeling was strategically centered on the macular fovea, extending to encompass the superotemporal and inferotemporal vascular arcades. Univariate analysis and multivariate logistic regression analysis were conducted to screen out the prognostic factors. Results: 36 eyes of 36 consecutive patients were analyzed in total. Best-corrected visual acuity (BCVA) improved significantly from 1.10 ± 0.61 logMAR to 0.78 ± 0.58 logMAR (p=0.031). 23 eyes (63.89%) had postoperative BCVA improved ≥ 2 Snellen lines. The mean central fovea thickness (CFT) decreased from 427.14 ± 255.91 μm to 155.85 ± 67.33 μm (p < 0.001). 18 and 16 eyes achieved partial and complete retinal reattachment, respectively, as follows. The twelfth month postoperatively was a threshold to influence the resolution of MF significantly, but it did not affect the visual outcome. Multiple logistic regression showed CFT (OR = 1.007, 95% CI = 1.001, 1.013, p value = 0.034) remained significant to predict the complete retina resolution. For visual acuity, integrated ellipsoid zone (EZ) band (OR = 0.239, 95% CI = 0.073, 0.783, p value = 0.018) might be a significant predictive factor. Subgroup analysis further indicated that in eyes with an intact EZ band, a poorer baseline BCVA was associated with an increase in postoperative BCVA (p=0.015). Conversely, in those with disrupted EZ band, all included factors showed no significant difference. Conclusion: The study observed trends in the recovery pattern of the retina following surgery and suggested potential factors that may be associated with improvements in both visual acuity and retinal reattachment. The findings may offer some guidance to ophthalmic surgeons in considering the timing of surgery, although further research is needed to confirm these trends as definitive predictors.

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Dataset Information

A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis.

Purpose

Methods

Results

Conclusions

Publications

A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis.

Similar Datasets

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