High-Mobility Group Box 1 Inhibitor BoxA Alleviates Neuroinflammation-Induced Retinal Ganglion Cell Damage in Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is a significant cause of vision loss and irreversible blindness worldwide. It is defined as retinal ganglion cell death and axon degeneration caused by injury. Optic nerve crush (ONC), a well-validated model of TON, activates retinal microglia and initiates neuroinflammation. High-mobility group box 1 (HMGB1), a non-histone chromosomal binding protein in the nucleus of eukaryotic cells, is an important inducer of microglial activation and pro-inflammatory cytokine release. The purpose of this study was to examine the protective effects and mechanism of the HMGB1 inhibitor BoxA to neuroinflammation-induced retinal ganglion cells (RGCs) damage in traumatic optic neuropathy. For that purpose, an optic nerve crush model was established in C57BL/6J mice at 10-12 weeks. Model mice received an intravitreal injection of PBS and the HMGB1 inhibitor BoxA. Our data demonstrated that HMGB1 expression increased after optic nerve crush. Retinal ganglion cell function and morphology were damaged, and retinal ganglion cell numbers were reduced after optic nerve crush. Intravitreal injection of BoxA after ONC can alleviate damage. Furthermore, BoxA reduced microglial activation and expression levels of nuclear factor κB (NF-kB), nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC) in experimental ONC mice. In summary, HMGB1 mediates NLRP3 inflammasome via NF-kB to participate in retinal inflammatory injury after ONC. Thus, intravitreal injection of BoxA has potential therapeutic benefits for the effective treatment of RGC death to prevent TON.

Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

PURPOSE: This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. METHODS: Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. RESULTS: Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p < 0.001) and significantly lower body weights (p < 0.001). Colour photography and FFA did not reveal any vessel abnormalities in the diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2+ pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. CONCLUSIONS: Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

RISK OF SILICONE OIL AS VITREOUS TAMPONADE IN PARS PLANA VITRECTOMY: A Systematic Review and Meta-Analysis.

PURPOSE: The authors examined the differences between silicone oil and other vitreous tamponades or placebo in performing pars plana vitrectomy. METHODS: This review and meta-analysis was conducted in accordance with the PRISMA guidelines. Seven databases and the reference lists of the retrieved randomized controlled trial articles were searched to identify eligible studies. The primary outcomes were the rate of redetachment after endotamponade removal, the rate of reoperation, and poor visual acuity. The secondary outcomes were adverse events and quality of life related to postoperative position. RESULTS: Ten articles (12 trials) were included. There were no significant differences between silicone oil and other agents in most of the primary and second outcomes. Only the risk of hypotony was found to be significantly lower when filling with silicone oil, compared with other agents. No trial reported the quality of life related to postoperative position. CONCLUSION: Based on the available studies, the authors conclude that there is no significant difference in the risk of poor outcomes between pars plana vitrectomy with silicone oil and that with other vitreous tamponades with different surgical histories.

Comparison of retinal parameters between rhesus and cynomolgus macaques.

Nonhuman primates are important research models for basic vision research, preclinical pathogenesis, and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between 10 healthy normal rhesus macaques (Macaca mulatta) and 10 cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The Heidelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinograms (mfERGs), and full-field electroretinograms (ff-ERGs). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thicknesses of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave was lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cell activity) and light-adapted 30-hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species, while the times to peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit times of the a- and b-waves in light-adapted 3.0 ERG (the single-flash cone response) were substantially different. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.

Factors affecting the severity and prognosis of visual damage in inhalational methanol poisoning.

Background/Aim: Inhalational methanol poisoning could cause severe damage to visual function. This study analyzed the prognosis of the correlation between the visual function and the relevant risk factors. Methods: In this retrospective study, 14 patients had confirmed inhalational methanol poisoning, resulting in visual impairment in both eyes. The following tests were performed: laboratory tests, best corrected visual acuity (BCVA), intraocular pressure, slit lamp, fundus photography, visual field (VF), pattern visual evoked potential (P-VEP), flash electroretinogram (F-ERG), optical coherence tomography (OCT), and orbital or cranial magnetic resonance imaging (MRI). Results: With active treatment, visual function improved to varying degrees in all 14 cases (28 eyes) in this study. The BCVA of 21 eyes declined to no light perception at the onset; 16 eyes showed different degrees of improvement after treatment, with the final BCVA (LogMar) mainly ranging from 2 to 3, and vision acuity stabilized after the 5th month. The VF pattern in the acute phase was mostly blind. Other VF patterns included the central visual island, large paracentral scotomas, hemipleural VF defects, and the temporal visual island. Retinal nerve fiber layer (RNFL) thickening was observed commonly in the acute phase (146.8 ± 33.2 µm), which subsided in the 1st month, showed dramatic thinning at the 3rd month, and then stabilized in the 5th month after onset. MRI showed that the main sites involved were optic nerve impairment, the optic disk, and retrobulbar segments. The basal ganglia region was the site most involved in the central nervous system (CNS). Conclusion: Inhalational methanol poisoning could lead to severe impairment of visual function, and the prognosis of visual acuity (VA) was highly relevant to the risk factors of duration of toxic exposure, delayed admission, and degree of acidosis.

Optic nerve head astrocytes contribute to vascular associated effects.

Purpose: This study was conducted in order to test the expression of vasoactive substances within rat lamina cribrosa (LC) and optic nerve head (ONH) astrocytes, so as to investigate the role and potential mechanism of ONH astrocytes in vascular associated effects. Methods: LC tissue sections and primary cultured ONH astrocytes were obtained from adult Sprague-Dawley (SD) rats. Immunofluorescent staining was then used to detect the expression of vasoactive substances. Hyperoxia exposure was carried out both in vivo and in vitro, after which nitric oxide (NO) levels in LC tissue and cell supernatant were detected. The variations of protein and gene expression associated with vasoactive substances were subsequently tested. ONH astrocytes and vascular smooth muscle cells (VSMCs) were then incubated in a direct co-culture manner. Morphological parameters of VSMCs were finally analyzed in order to evaluate cell contraction. Results: Endothelin-1 (ET-1), nitric oxide synthase (NOS) and renin-angiotensin system (RAS) were detected in both LC tissue and ONH astrocytes. Retinal vessel diameter was found obviously decreased following hyperoxia exposure. Moreover, hyperoxia inhibited NO production both in vivo and in vitro. ET-1 and RAS elements were observed to be upregulated, whereas NOS was downregulated. In ONH astrocytes and VSMCs co-culture system, the length-to-width ratio of VSMCs was shown to significantly increase on days 3 and 7 in hyperoxia compared with normoxia. Conclusions: There is an abundance of expression of vasoactive substances within LC tissue and ONH astrocytes. The contractile response of VSMCs in the co-culture system provided direct evidence for the involvement of ONH astrocytes in vascular associated effects, which may signify a potentially novel direction for future research.

A Pilot Clinical Study of Intravitreal Injection of Artesunate for Ocular Neovascularization.

Purpose: To evaluate the efficacy and primary safety of treatment with artesunate in reducing ocular neovascularization in humans. Methods: Five patients with corneal, iris, and retinal neovascularization and no light perception were treated with intravitreal injections of artesunate 80 µg. Visual acuity, anterior segment photography, fundus fluorescein angiography, and optical coherence tomography were used to evaluate efficacy, while intraocular pressure (IOP) and lens opacity degree were employed to evaluate safety. The primary endpoint was attenuation of neovascularization as determined at 24 weeks, with the last posttreatment follow-up at 52 weeks. Results: Corneal and iris neovascularization, which were secondary to fundus ischemic diseases and retinal neovascularization in all 5 patients, were attenuated after 1 or 2 injections by the 52-week follow-up. Retinal neovascularization was also attenuated, and papilledema was alleviated. The average IOP fell from 25.5 mmHg to 17.66 mmHg. Conclusions: This pilot study determined that intravitreal artesunate injection is efficacious for reducing corneal, iris, and retinal neovascularization. These results indicate that this drug may be a novel alternative to the currently popular antivascular endothelial growth factor drugs used to suppress ocular neovascularization and improve visual function.

Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation combination therapy for macular edema secondary to retinal vein occlusion: preliminary report.

AIM: To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor (VEGF) agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and retinal vessel oxygenation were examined over 12mo. RESULTS: Patients received 1.43±0.81 anti-VEGF injections. Mean baseline and 12-month logMAR BCVA were 0.96±0.51 (20/178) and 0.31±0.88 (20/40), respectively, in eyes with central retinal vein occlusion (CRVO) (P<0.00), and 1.02±0.45 (20/209) and 0.60±0.49 (20/80), respectively, in eyes with branch retinal vein occlusion (BRVO) (P<0.00). At 12mo, CRT had significantly decreased in eyes with CRVO (P<0.00) and BRVO (P<0.00). Venous oxygen saturation had significantly increased in eyes with CRVO (P<0.00) and BRVO (P<0.00). No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION: Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO-associated ME.

Macular Retinal Vessel Oxygen Saturation Elevation in Chinese Central Serous Chorioretinopathy.

PURPOSE: To evaluate the retinal vessel oxygen saturation in central serous chorioretinopathy (CSC) cases among the Chinese. METHODS: Relative oxygen saturation of retinal blood vessels was measured in 33 Chinese patients with single-eye CSC using the Oxymap T1 retinal oximeter. The contralateral eyes were the control. The mean saturation of the retinal arteriole (AS) and venule (VS), arteriovenous difference (AVS), and arteriole and venule diameters (AD, VD) was analyzed in the optic disc area and macular region. RESULTS: In the optic disc area, the inferotemporal quadrant (TI) AS (93.2 ± 10.2%) and inferonasal quadrant (NI) VS (61.3 ± 7.3%) were higher in the affected eyes than in the contralateral eyes (88.7 ± 7.7% and 56.9 ± 6.5%) and AVS in NI (36.7 ± 10.4%) decreased compared to the contralateral eyes (41.5 ± 11.2%). The VD in TI was expanded (19.9 ± 2.5 pixels versus 18.1 ± 3.4 pixels). Around the macular region, AS was 93.6 ± 7.6%, higher than in the contralateral eyes (89.5 ± 6.3%). No other significant changes were found. CONCLUSIONS: AS increased in the TI, and VS decreased in the NI in the eyes with CSC. In addition, AS also increased around the macular region, suggesting that these are contributors to CSC pathophysiology.

The efficacy and safety of a novel posterior scleral reinforcement device in rabbits.

PURPOSE: To evaluate the efficacy and safety of posterior scleral reinforcement (PSR) device for myopia suppression in rabbits' eyes. METHODS: PSR surgery was performed on the normal 12 8-week-old New Zealand white rabbits' right eyes. To determine efficacy of the device, ophthalmic examination would be taken at pre-operation and post-operation (1 week, 1 month, 3 months, 6 months, and 1 year), such as A-ultrasound, diopter and B-ultrasound. Evaluation of safety were based on the following indicators: intraocular pressure (IOP), slit lamp, fundus photography, fundus fluorescein angiography and pathological examination after surgery. The efficacy and safety of PSR device were evaluated by comparison (treated eyes and contralateral eyes) of pre and post-operation. RESULTS: The novel PSR device could significantly shorten axial length (preoperative axial length: 16.36 ± 0.14 mm, postoperative 1 week, 1 month, 3 months, 6 months and 1 year axial lengths: 15.03 ± 0.28 mm, 15.23 ± 0.32 mm, 15.39 ± 0.31 mm, 15.45 ± 0.22 mm and 15.45 ± 0.22 mm; P=0.00037<0.001) in the treated eyes (right eyes) after surgery. At different postoperative time points, the B-ultrasound images showed that the PSR located in appropriate position and supported the posterior sclera very well. At the same time, IOP of treated eyes kept a relatively stable level (preoperative IOP: 12.56 ± 2.01 mmHg, postoperative IOP: ranging from 11.33 ± 1.23 mmHg to 13.44 ± 2.19 mmHg, P>0.05) post-operation 1 year. During observation period, there was no significant inflammatory reaction and complications such as anterior chamber flare, empyema, endophthalmitis, vitreous hemorrhage, retina detachment and retinal choroid neovascularization by slit lamp, fundus photography and fundus fluorescein angiography. In addition, there were no pathologic changes be found by comparison treated eyes group and contralateral group eyes based on pathological examinations. CONCLUSIONS: In vivo study, effectively and safely, the novel PSR device can inhibit rabbits' axial length elongation during postoperative 1 year. This study demonstrates that this novel PSR could be a potential treatment approach for myopia.