Application of Proteomics Analysis and Animal Models in Optic Nerve Injury Diseases.

Optic nerve damage is a common cause of blindness. Optic nerve injury is often accompanied by fundus vascular disease, retinal ganglion cell apoptosis, and changes in retinal thickness. These changes can cause alterations in protein expression within neurons in the retina. Proteomics analysis offers conclusive evidence to decode a biological system. Furthermore, animal models of optic nerve injury made it possible to gain insight into pathological mechanisms, therapeutic targets, and effective treatment of such injuries. Proteomics takes the proteome as the research object and studies protein changes in cells and tissues. At present, a variety of proteomic analysis methods have been widely used in the research of optic nerve injury diseases. This review summarizes the application of proteomic research in optic nerve injury diseases and animal models of optic nerve injury. Additionally, differentially expressed proteins are summarized and analyzed. Various optic nerve injuries, including those associated with different etiologies, are discussed along with their potential therapeutic targets and future directions.

Retina Vascular Structures near the Optic Disc and in the Macula in Primary Angle-Closure Suspects.

INTRODUCTION: The main aim of this article was to study the retinal peripapillary and macular vascular structures in eyes with primary angle-closure suspects (PACS) using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, control and PACS subjects were recruited from a community screening. Only one eye per subject was used for analysis. All participants underwent a questionnaire survey, physical and ophthalmic examinations, ocular biometry measurements, and OCTA. We compared basic demographics and vessel structure parameters between control and PACS eyes. Univariate and multivariate linear regression analyses were performed to investigate factors associated with vascular parameters in both groups. RESULTS: Data from 254 subjects including 155 PACS and 99 controls were analyzed. In the peripapillary region, PACS eyes showed similar retina nerve fiber layer (RNFL) and vessel densities (VDs) including and excluding large vessels compared to control eyes. Compared to control eyes, all macular OCTA parameters showed significant differences in PACS eyes, including decreased superficial VD (p = 0.006) and deep VD (p = 0.004), larger fovea avascular zone (FAZ) area (p = 0.006), and longer FAZ perimeter (p = 0.004). Gender (p = 0.039), age (p < 0.001), and Garway-Heath superior hemisphere RNFL (p < 0.001) were risk factors influencing optic disc VD excluding large vessels. Axial length was the major factor affecting macula superficial and deep VDs (p = 0.004 and 0.001 respectively), while PACS was an independent factor associated with larger FAZ perimeter (p = 0.046). CONCLUSION: While PACS and control eyes have comparable RNFL and vascular structure around the optic nerve head, macular vascular structures are significantly different.

Ganglion Cell Complex Parameters in Primary Angle Closure Suspects.

INTRODUCTION: This study aimed to investigate the ganglion cell complex (GCC) parameters in primary angle closure suspects (PACS) and identify the related factors. METHODS: A total of 731 subjects, including 289 subjects with PACS and 442 subjects without PACS, underwent RTVue XR OCT. GCC parameters were compared between the two groups. The linear mixed-effects model was performed to evaluate the relationships between the GCC parameters and related factors. RESULTS: Significant differences were found in gender, age, spherical refractive error, height, waist, anterior chamber depth, lens thickness, axial length, superior GCC thickness, ganglion cell complex focal loss volume, ganglion cell complex global loss volume, and ganglion cell complex root mean square between PACS and normal controls. The linear mixed-effects model showed that age (p = 0.008) and blood glucose (p = 0.001) were negatively correlated with average GCC thickness in PACS subjects, and PACS (p = 0.036) and age (p < 0.001) were the key influencing factors for average GCC thickness. CONCLUSION: GCC parameters in PACS subjects are different from those in normal controls. Careful explanation should be considered when evaluating changes of GCC parameters in patients with PACD.

WITHDRAWN: Exosomes derived from BDNF-expressing 293T attenuate ischemic retinal injury in vitro and in vivo.

This paper was originally published in Aging Advance Online Publications on November 29, 2020. In compliance with Aging's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Aging internal or any external indexes or archives.

Proteomic analysis of underlying apoptosis mechanisms of human retinal pigment epithelial ARPE-19 cells in response to mechanical stretch.

Our previous study demonstrated mechanical stretch (MS) could induce the apoptosis of retinal pigment epithelial (RPE) cells, but the related mechanisms remained unclear. This study was to characterize the protein expression profile in RPE cell line ARPE-19 exposed to MS, cytochalasin D (CD; an inhibitor of actin polymerization) or CD + MS at 2-time points (6, 24 hr; n = 3, at each time point) by using proteomics technique. Our data highlighted that compared with control, ECE1 was continuously downregulated in ARPE-19 cells treated by MS or CD + MS from 6 to 24 hr. Function and protein-protein interaction network analyses showed ATAD2 was downregulated in all three treatment groups compared with control, but successive upregulation of RPS13 and RPL7 and downregulation of AHSG were specifically induced by MS. ATAD2 was enriched in cell cycle; AHSG was associated with membrane organization; RPS13 and RPL7 participated in ribosome biogenesis. Furthermore, transcription factor CREB1 that was upregulated in MS group at 24 hr after treatment, may negatively regulate ATAD2. The expressions of all crucial proteins in ARPE-19 cells were confirmed by western blot analysis. Overexpression of ATAD2 and AHSG were also shown to reverse the apoptosis of ARPE-19 cells induced by MS or CD + MS, with significantly decreased apoptotic rates and caspase-3 activities. Accordingly, our findings suggest downregulation of ATAD2 and AHSG may be potential contributors to the apoptosis of RPE cells induced by MS. Overexpression of them may represent underlying preventive and therapeutic strategies for MS-induced retinal disorders.

Partial Optic Nerve Transection in Rats: A Model Established with a New Operative Approach to Assess Secondary Degeneration of Retinal Ganglion Cells.

Previous studies have shown that the secondary degeneration of retinal ganglion cells (RGCs) occurs commonly in glaucoma. Partial optic nerve transection is considered a useful and reproducible model. Compared with other optic nerve injury models used commonly for assessing secondary degeneration, e.g. complete optic nerve transection and optic nerve crush models, the partial optic nerve transection model is superior as it distinguishes primary from secondary degeneration in situ. Therefore, it serves as an excellent tool for evaluating secondary degeneration. This study describes a novel operative approach of partial optic nerve transection by directly accessing the area of the retrobulbar optic nerve through the orbital lateral wall of the eyeball. Moreover, we present a newly designed, low cost surgical instrument to assist with transection. As demonstrated by the representative results in distinguishing the boundary of primary and secondary injury areas, the new approach and instrument ensures high efficiency and stability of the model by providing adequate space for surgical operation. This in turn makes it easy to separate the meningeal sheath and ophthalmic vessels from the optic nerve before transection. An additional benefit is that this space-saving operative approach improves the investigators' ability to administer drugs, carriers, or selective RGC tracers to the stump of the partially transected optic nerve, allowing the exploration of mechanisms behind secondary injury in RGCs, in a new way.

Detection of early neuron degeneration and accompanying glial responses in the visual pathway in a rat model of acute intraocular hypertension.

Transsynaptic degeneration has been implicated in patients with primary open angle glaucoma (POAG) and animal models of chronic intraocular hypertension. Whether the sustained intraocular pressure (IOP) elevation is necessary for the induction of transsynaptic changes in the brain remains unclear. The aim of this study is to characterize the effects of acute and transient intraocular hypertension on the visual pathway of rats. Acute intraocular hypertension was induced in the right eye by anterior chamber perfusion. At 1 day, 3 days, 1 week, 2 weeks and 4 weeks after the operation, neuronal degeneration and glial responses in the retina, dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) were assessed using Nissl staining and immunohistochemistry. TUNEL staining was also performed to detect the neuronal apoptosis in the brain. At the first day after the operation, no obvious neuronal changes were detected in the retina or the brain. At 3 days, 46% of the retinal ganglion cells (RGCs) were lost. Atrophy of the contralateral optic tract was also observed. Meanwhile, the cross-sectional area of neurons in the contralateral dLGN and SC was decreased, while cell density in the same regions was increased. Glial activation in the retina occurred much earlier than the RGC loss. Co-expression of glial fibrillary acid protein (GFAP) and glutamine synthetase (GS) was observed in the end-feet and processes of Müller cells at 1 day after the operation. GFAP immunoreactivity was remarkably increased in the contralateral dLGN and SC at 3 days. It also showed a good co-localization with GS. All of aforementioned changes gradually progressed and persisted for the whole observation period. No TUNEL-positive cells were detected in the dLGN and SC at any post-operative time point. Taken together, these results illustrate that acute and transient intraocular hypertension is able to induce early onset and long-lasting neurodegenerative changes and the accompanying glial activation in the visual pathway. Brain changes may occur in parallel with the RGC loss. Reactive glial cells in the brain may participate in the clearance of aberrantly released glutamate and may serve as a sensitive marker of neuronal injury. Neuroprotection of the entire visual pathway and glia-target therapies may bring new insights into the glaucoma treatment.