Background: Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown. Methods: A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca²⁺ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina. Results: We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner. Conclusions: These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.

Retinal inflammation is a devastating pathological process in ocular diseases. Functional impairment of retinal pigment epithelium (RPE) is associated with inflammatory retinal diseases. Enhancing the protective axis namely ACE2/Ang-(1-7)/Mas by activation of ACE2 presents anti-inflammatory properties. We investigated whether diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, prevented lipopolysaccharide (LPS)-induced inflammatory response by activating the protective axis and whether the effect was mediated by inhibiting the mitogen-activated protein kinase (MAPK) and the nuclear factor-κB (NF-κB) pathways. Cell counting kit-8 (CCK-8) assay and real-time PCR were used to determine the optimum concentration and incubation time of DIZE. ARPE-19 cells and primary cultured human retinal pigment epithelia (hRPE) were incubated with or without 10 μg/mL DIZE for 6 h before stimulated with 5 μg/mL LPS for 24 h. The mRNA expression of inflammatory cytokines, AT1R, and AT2R was analyzed. The protein level of inflammatory cytokines, Ang II, and Ang-(1-7) was detected. Phosphorylation of p38 MAPK, extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphorylated transcription inhibition factor-κB-α (p-IκB-α) were measured. Inhibitors of MAPKs and NF-κB were added to verify the involvement of these pathways. A small interfering RNA (siRNA) targeted to ACE2 and a selective Ang-(1-7) antagonist A779 was used to confirm the role of ACE2 and the involvement of ACE2/Ang-(1-7)/Mas axis. DIZE remarkably increased the expression of ACE2 and inhibited the expression of IL-6, IL-8, and MCP-1 at both mRNA and protein levels in both RPE cell lines stimulated with LPS. Inhibitors of p38, ERK1/2, JNK, and NF-κB significantly decreased LPS-induced overproduction of IL-6, IL-8, and MCP-1. DIZE reduced the expression of Ang II and AT1R, whereas increased Ang-(1-7). Furthermore, DIZE downregulated the phosphorylation of p38MAPK, ERK1/2, JNK, and the activation of NF-κB upon stimulation with LPS. Downregulating ACE2 and pre-treatment with A779 abrogated the effects of DIZE on production of cytokines, the expression of Ang II, Ang-(1-7), AT1R, phosphorylation of MAPKs and activation of NF-κB. DIZE inhibits LPS-induced inflammatory response by activating ACE2/Ang-(1-7)/Mas axis in human RPE cells. The protective effect is mediated by inhibiting the p38MAPK, ERK1/2, JNK, and NF-κB pathways.

Purpose. Uveitis is a common cause of vision loss. The renin angiotensin system (RAS), which plays a vital role in cardiovascular system, is a potent mediator of inflammation and has been implicated in the pathogenesis of uveitis. A newly identified axis of RAS, ACE2/Ang-(1-7)/Mas, has emerged as a novel target because it counteracts the deleterious effect of angiotensin II. The purpose of this study was to investigate the effect of endogenous ACE2 activation in preventing endotoxin-induced uveitis (EIU) in mice. Methods. ACE2 activator diminazene aceturate (DIZE) was administered both systemically and locally. For systemic administration, female BALB/c mice received intraperitoneal injection of DIZE (60 mg/kg body weight [BW]) for 2 days prior to lipopolysaccharide (LPS) intravitreal injection (125 ng) to induce uveitis. For local study, DIZE was given at 0.5, 0.1, and 0 mg/mL as eyedrops six times per day for 2 days before LPS injection. The anterior segment of the mice was examined at 12, 24, 48, and 72 hours after LPS injection, and clinical scores were determined at the same time. Morphology and infiltrating inflammatory cells were evaluated after 24 hours. The mRNA levels of inflammatory cytokines were analyzed by real-time RT-PCR. ACE2 activity was determined using a self-quenching fluorescent substrate. Results. At 24 hours, the clinical score of mice treated with DIZE systemically was significantly lower (mean, ∼1.75) than the saline vehicle group (mean, ∼4) (P < 0.001). Histological examination showed 63.4% reduction of infiltrating inflammatory cells in the anterior segment and 57.4% reduction in the posterior segment of DIZE-treated eyes. The number of CD45⁺ inflammatory cells in the vitreous of the DIZE-treated group was decreased (43.3%) compared to the vehicle group (P < 0.01). The mRNA levels of inflammatory cytokines were significantly reduced in the DIZE-treated group (P < 0.01, P < 0.001). The number of infiltrating inflammatory cells was also significantly reduced in eyes that received topical administration of DIZE: 73.8% reduction in the 0.5 mg/mL group and 51.7% reduction in the 0.1mg/mL group compared to the control group. DIZE treatment resulted in significantly increased ACE2 activity in the retina (P < 0.001). Conclusions. Endogenous ACE2 activation by DIZE has a preventive effect on LPS-induced ocular inflammation in the EIU mouse model. These results support the notions that RAS plays a role in modulating ocular immune response and that enhancing ACE2 provides a novel therapeutic strategy for uveitis.

Background: Despite the increasing recognition of the public health value of social media platforms, TikTok short videos focusing on adolescent vision health have not received much attention. We aimed to evaluate the content, sources, and information quality of myopia-related videos on TikTok.Methods: The top 200 most-liked myopia-related videos on the Chinese version of TikTok were queried and screened on March 12, 2022. The descriptive characteristics, contents, and sources of the selected 168 videos were obtained, and their overall quality, reliability, understandability, and actionability were assessed using the validated scoring instruments DISCERN and PEMAT-A/V.Results: Medical professionals were the main source (45.8%, 77/168) of videos. Misinformation (10.1%, 17/168) was mainly attributable to for-profit organizations (20%, 3/15) and individual non-medical users (31.3%, 10/32). However, their videos enjoyed the highest numbers of “likes,” “comments,” and “shares” (P < 0.05). The mean reliability and overall quality regarding treatment choice were (2.5 ± 0.5) and (3.1 ± 0.9), respectively. Videos on TikTok showed relatively high understandability (84.7%) and moderate actionability (74.9%). Video producers tended to partly or fully provide information regarding management (81.5%, 137/168) and outcome (82.1%, 138/168), and to ignore or only slightly mention content related to definition (86.9%, 146/169) and signs (82.1%, 138/168). The five video sources showed significant differences in the prevalence of misleading information (P < 0.001), publication reliability (P < 0.001), overall quality (P = 0.039), content score (P = 0.019), and understandability (P = 0.024).Conclusion: Considering the moderate-to-poor reliability and variable quality across video sources, the substantial myopia-related content on TikTok should be treated with caution. Nevertheless, TikTok videos may serve as a surrogate or supplement for information dissemination if providers can ensure more comprehensive and accurate content.

Objective: To summarize updated evidences on the efficacy and safety of adalimumab (ADA) in the treatment of patients with non-infectious uveitis. Patients and methods: A systematic search between January 2000 and September 2017 was conducted using PubMed, Embase, and Cochrane libraries. We investigated control of inflammation, improvement of visual acuity (VA), corticosteroid-sparing effect, and adverse events (AEs) or serious adverse events. Results: Three randomized clinical trials (RCTs) and 20 non-RCTs were included and analyzed. The pooled proportions of inflammation control were 74% (95% CI 64%–82%) and 79% (95% CI 69%–87%) in groups of ≤6- and ≥12-months follow-up durations. No significant difference was found between the two groups (χ² = 0.920, p = 0.337). Analysis of subgroups classified by degree of being treatment-naïve for anti-TNFα agents showed the inflammation control reached a high of 87% (95% CI 80%–92%) when subjects were “almost naïve” to anti-TNFα before ADA treatment. VA was improved by three or more lines in 41.3% (52/126) eyes, and was equal to or better than the baseline in 88.8% (142/160) eyes. Corticosteroid sparing was observed in 82.0% (91/111) of the patients; among them, 48.8% (40/82) discontinued use of corticosteroid completely. Minor drug-related adverse events were reported. The treatment effects of ADA were generally consistent in the three RCTs, and ADA reduced the risk of treatment failure by 43%–75%. Conclusion: The current review provided evidences that ADA might be a promising choice in reducing inflammatory activity, gaining VA, and sparing corticosteroid use with minor AEs when applied in treating non-infectious uveitis.