Overexpression of Optic Atrophy Type 1 Protects Retinal Ganglion Cells and Upregulates Parkin Expression in Experimental Glaucoma

Glaucoma is a neurodegenerative disease that features progressive loss of retinal ganglion cells (RGCs). Increasing evidences have revealed that impaired mitochondrial dynamics occurs early in neurodegenerative diseases. Optic Atrophy Type 1 (OPA1), a mitochondrial fusion protein, has recently been suggested to be a mitophagic factor. Our previous studies found that glaucomatous retinal damage may be ameliorated by an increase in mitochondrial OPA1. In this study, we explored the mechanism involved in OPA1 mediated neuroprotection and its relationship with parkin dependent mitophagy in experimental glaucoma models. Our data showed that overexpression of OPA1 by viral vectors protected against RGC loss, attenuated Bax expression, and improved mitochondrial health and mitochondrial surface area. Parkin expression and the number of mitophagosomes were upregulated in OPA1 overexpressed RGCs under glutamate excitotoxicity. While knockdown of OPA1 by siRNA decreased protein expression of parkin in RGCs under glutamate excitotoxicity. Two weeks after intraocular pressure (IOP) elevation, the LC3-II/I ratio and the LAMP1 expression were increased in OPA1 overexpressed optic nerve. These findings suggest that OPA1 overexpression may protect RGCs by ways of enhancing mitochondria fusion and parkin mediated mitophagy. Interventions to promote mitochondrial fusion and mitophagy may provide a useful strategy to battle against glaucomatous RGC loss

Optic disc shape in patients with long-lasting unilateral esotropia and exotropia

Background: Horizontal eye movements have been proposed to induce biomechanical stress and strain on optic nerve head. Since strabismus may lead to sustained adduction or abduction, we investigate the effects of long lasting unilateral horizontal strabismus on the morphology of optic disc. Methods: The observational cross-sectional study included patients with unilateral constant horizontal strabismus lasting for more than two years. The patients underwent an ophthalmological examination including refraction and morphometry of the optic nerve head. A prism cover test using right angle glass prism was performed to measure the magnitude of the ocular deviation. Results: The study included 70 patients with a unilateral constant strabismus (35 esotropic patients, 35 exotropic patients) with a mean age of 26 ± 19 years, mean refractive error of − 0.72 ± 3.3 diopters, mean axial length of 23.8 ± 1.7 mm, and a mean angle of deviation of 87 ± 36 prism diopters (Chinese right-angle glass method) in the esotropic group and − 97 ± 29 prism diopters in the exotropic group. In the whole study population and taken separately in the esotropic group and exotropic group, the disc ovality index (defined as ratio of minimal-to-maximal optic disc diameter) did not differ significantly between the deviating eyes and the contralateral fixating eyes (all P > 0.05). As a corollary, the disc ovality index and the prevalence of parapapillary beta/gamma zone did not differ significantly between the esotropic group and the exotropic group (all P > 0.05). Conclusions: Optic disc ovality did not differ markedly among long-lasting esotropic eyes, exotropic eyes, and non-strabismic eyes. It suggests that optic disc shape may not be markedly influenced in non-highly myopic eyes by a potential backward pull of the optic nerve on the optic disc structures in adduction or abduction