Circular RNA expression profile and functional analysis of circUvrag in light-induced photoreceptor degeneration.

BACKGROUND: Circular RNAs (circRNAs) are implicated in retinal pathophysiology; however, their expression profiles and functions in photoreceptor apoptosis are largely unknown. We explored circRNA-expression profiles and circUvrag (host gene: Uvrag, ultraviolet radiation resistance associated gene) function in light-induced photoreceptor apoptosis. METHODS: Sprague-Dawley rats and 661 W photoreceptor cells were exposed to blue light to establish light-induced photoreceptor degeneration. Differentially expressed circRNAs were identified using microarrays. Potential functions of dysregulated circRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircUvrag expression and localization were evaluated using quantitative RT-PCR and fluorescence in situ hybridization, respectively. CircUvrag overexpression and knockdown were induced using a plasmid and a small interfering RNA, respectively, and retinal function and structure were assessed using scotopic electroretinography, haematoxylin-eosin staining, and TUNEL staining. Microglial migration was assessed using IBA1 immunostaining. The apoptosis ratio of photoreceptor cells in vitro was detected using flow cytometry. RESULTS: We identified 764 differentially expressed circRNAs, which were potentially related with the development of retinal structures, including neurons, dendrites, and synapses, and might participate in nervous-system pathophysiology. Light exposure enriched circUvrag in the cytoplasm of photoreceptors in the outer nuclear layer (ONL). CircUvrag knockdown decreased photoreceptor apoptosis and microglial migration to the ONL after light exposure, preserving ONL thickness and a-wave amplitude. In vitro, circUvrag knockdown inhibited photoreceptor apoptosis, although circUvrag overexpression slightly promoted photoreceptor apoptosis. CONCLUSIONS: CircUvrag knockdown attenuated light-induced photoreceptor apoptosis, and might be a potential target in retinal degeneration.

Structural and functional analysis of multiple subretinal fluid blebs after successful surgery for rhegmatogenous retinal detachment.

INTRODUCTION: This retrospective study investigated the clinical characteristics of multiple subretinal fluid blebs (MSFBs) after successful surgery for rhegmatogenous retinal detachment (RRD), and explored the association between MSFB with best-corrected visual acuity (BCVA) and metamorphopsia. METHODS: The study comprised 206 patients after successful surgery for RRD, with 58 and 148 eyes undergoing, respectively, scleral buckling (SB) and pars plana vitrectomy (PPV). The clinical characteristics of MSFBs were analyzed by optical coherence tomography (OCT). The choroidal vessels in some cases were evaluated with OCT angiography. M-charts were used to determine the metamorphopsia. RESULTS: MSFBs occurred in 17 (29.3%) and 8 (5.4%) eyes given SB and PPV, respectively. MSFBs appeared 5.6 ± 5.5 weeks after surgery and required 34.9 ± 13.8 weeks to disappear. Disrupted external limiting membrane and ellipsoid zone could still be seen in 83.3% and 66.7% of the patients 12 months after surgery; these rates were significantly higher than those of patients without MSFBs (P = 0.047, 0.022, respectively). Twelve months post-surgery, BCVA and metamorphopsia scores of the patients with MSFBs were statistically comparable to those of the controls. CONCLUSIONS: MSFBs occur more commonly after SB than PPV. MSFBs may delay the recovery of the outer retina structure, but do not affect postoperative BCVA and metamorphopsia.

Synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model.

Purpose: To explore synaptic changes and the response of microglia in a light-induced photoreceptor degeneration model. Methods: Sprague-Dawley rats were euthanized 1 h, 1 day, 3 days, 7 days, and 14 days after being exposed to intense blue light for 24 h. Hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate changes in the outer nuclear layer (ONL). Transmission electron microscopy (TEM) was applied to observe the ultrastructural changes in the synapses between the photoreceptors and second-order neurons. Western blotting was conducted to evaluate specific proteins, including postsynaptic density-95 (PSD-95), metabotropic glutamate receptor 6 (mGluR6), synapsin I, and synaptophysin. Immunofluorescence of CD11b and PKC-α or mGluR6 was used to explore the spatial relationships between microglial processes and synaptic elements. Immunoelectron microscopy of PSD-95 was performed to further confirm its engulfment of synaptic materials. Results: H&E and TUNEL staining showed that the thickness of the ONL decreased markedly, and the number of apoptotic photoreceptors peaked at day 1. TEM revealed darkened photoreceptor terminals and that ribbons of them were floating in the cytoplasm, coinciding with the downregulation of PSD-95 and mGluR6. Downstream synaptic protein synapsin I and synaptophysin exhibited upregulation in the inner plexiform layer. Activated microglia migrated to the outer retina, and their processes were found in close proximity to synapses in the outer plexiform layer under light and electron microscopy levels. Double immunostaining of CD11b and mGluR6 showed colocalization. PSD-95-immunoreactive electron-dense materials were observed inside the microglia suggesting engulfment of synaptic components. Conclusions: The study showed that there are early synaptic impairment and late compensatory changes in downstream synapses in this photic injury model. Activated microglia touched and directly engulfed synaptic materials. Microglia may play a role or a partial role in synaptic changes.

THE EVOLUTION OF ISOLATED NEOVASCULAR TUFTS ("POPCORN") IN RETINOPATHY OF PREMATURITY.

PURPOSE: To explore the natural evolution of isolated neovascular tufts ("popcorn") in retinopathy of prematurity (ROP) and its significance in the progression of acute ROP. METHODS: In this retrospective case series, 89 infants (89 eyes) in total having acute ROP were analyzed during serial retinal examinations with a RetCam III wide-angle fundus imaging system, among which 53 eyes were observed to have popcorn and 36 eyes did not. The clinical outcomes of the popcorn (+) group and the popcorn (-) group were compared. RESULTS: Popcorn was located only in Zone II, Stage 2 ROP, primarily in the temporal field (65%). It appeared at a mean postmenstrual age of (37.6 ± 1.3) weeks, disappeared at (41.0 ± 2.2) weeks, and lasted for (2.8 ± 1.1) weeks. The popcorn (+) group had a significantly higher natural regression incidence than the popcorn (-) group (P < 0.05). The laser-treated eyes in the popcorn (+) group had earlier presentations (36.4 ± 0.7 vs. 38.2 ± 1.3 weeks) and shorter existences (1.5 ± 0.5 vs. 3.2 ± 0.9 weeks) of popcorn than the regressed eyes (P < 0.01, respectively). CONCLUSION: Popcorn is generally a "benign" indicator of the regression of ROP. The early presentation (

Optical coherence tomography features of retinal lesions in Chinese patients with endogenous Candida endophthalmitis.

BACKGROUND: To evaluate the optical coherence tomography (OCT) features of retinal lesions in Chinese patients with endogenous Candida endophthalmitis (ECE). METHODS: We performed a retrospective review of patients diagnosed with ECE at one medical center. The medical records of the patients including predisposing risk factors, treatment and visual acuity were reviewed. And we focused on the analysis of OCT images of retinal lesions before and after treatment. RESULTS: A total of 16 Chinese patients (22 eyes) were included in this study. The most frequent predisposing risk factors were intravenous use of corticosteroids or antibiotics, lithotripsy for urinary calculi, and diabetes. After treatment, visual acuity was improved in 13 (59.1%) of the 22 eyes, and remained the same in the other 9 (40.9%) eyes. Pre-treatment OCT images obtained at presentation were available for 17 of the 22 eyes. Four types of the OCT manifestations of retinal lesions were identified: type 1 (subretinal macular lesions), type 2 (lesions are located in the inner retinal layer), type 3 (lesions involve the full-thickness retina and accompanied with macular edema), type 4 (sub-inner limiting membrane lesions). Pre-treatment OCT imaging of the 17 eyes revealed five as type 1, four as type 2, six as type 3, and two as type 4. After treatment, OCT images revealed epiretinal membrane and subretinal fibrosis as the most common post-treatment complications of ECE. Epiretinal membrane was detected in 2/4 type 2 lesions, in 4/6 type 3 lesions, and in 1/2 type 4 lesions, while subretinal fibrosis was mainly seen in type 1 lesions (4/5). Among the types, visual prognosis was best in eyes with type 2 lesions. CONCLUSIONS: In this case series, the OCT manifestations of retinal lesions in ECE could be classified into four types. The post-treatment OCT manifestations were different in four types of lesions. We preliminarily found that the OCT morphology of retinal lesions was associated with the visual prognosis of ECE.

Lentivirus vector-mediated knockdown of Sox9 shows neuroprotective effects on light damage in rat retinas.

Purpose: To investigate whether reduced Sox9 function exerts neuroprotection in light-induced retinal damage in rats and to explore the potential mechanism behind it. Methods: Retinal light damage was used as a model for retinal degeneration. Two weeks before light damage in adult Sprague Dawley (SD) rats, the Sox9-shRNA lentiviral vector was intravitreally injected. On days 3, 7, and 14, retinal function was assessed using electroretinography (ERG), and the thickness of the outer nuclear layer (ONL) was measured in hematoxylin and eosin (HE) stained sections. The protein levels of glial fibrillary acidic protein (GFAP), vimentin, nestin, and chondroitin sulfate proteoglycans (Cspgs), which are related to gliosis and extracellular matrix (ECM) remodeling, were observed using western blot analysis. The expression of GFAP was further evaluated by immunohistochemistry. Results: On days 3, 7, and 14 after light damage, the thickness of the ONL and the amplitudes of the ERG waves were significantly better preserved in the Sox9-shRNA group when compared with the control group. The protein levels of GFAP, vimentin, nestin, and Cspgs were significantly downregulated in the Sox9-shRNA group. Furthermore, the staining intensity and the spatial distribution of GFAP in the retinas were also obviously attenuated at every studied time point. Conclusions: Intravitreal injection of the Sox9-shRNA lentiviral vector preserved rat retinal morphology and function after light damage and downregulated GFAP, vimentin, nestin, and Cspgs, which are related to Müller cell gliosis and ECM remodeling. The results indicate that Sox9 might be a potential therapeutic target for retinal degenerative diseases.

Expression of CCL2 and its receptor in activation and migration of microglia and monocytes induced by photoreceptor apoptosis.

Purpose: To explore the effect of the CCL2 and CCR2 system on the activation and migration of microglia and monocytes in light-induced photoreceptor apoptosis. Methods: At 1 day, 3 days, 7 days, and 14 days after light exposure, OX42 and ED1 immunostaining were used to label the activation and migration of microglia and monocytes. Double immunostaining of CCL2 with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), OX42, or glial fibrillary acidic protein (GFAP) was applied to explore the relationships among CCL2, apoptotic photoreceptors, activated microglia and monocytes, and macroglial cells (Müller cells and astrocytes). Real-time PCR was used to evaluate the mRNA levels of retinal CCL2 and CCR2 and the proinflammatory factors interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha. Results: Real-time PCR analyses showed that CCL2 and CCR2 expression gradually increased after light exposure and peaked at 3 days, coinciding with the infiltration of OX42-positive cells and the expression of IL-1 beta and TNF-alpha in the outer retina. Double immunostaining of CCL2 with TUNEL revealed that CCL2 was expressed robustly in about 30% of the apoptotic photoreceptors at the early stage. As degeneration progressed, immunostaining of CCL2 with OX42 showed that activated and migrated microglia and monocytes expressed CCL2. At the late stage, Müller cells became the main source of CCL2, which was illustrated by CCL2 immunostaining with GFAP. Conclusions: Light exposure led to apoptosis of photoreceptors, which expressed CCL2, accelerating an inflammation-mediated cascade by activating and attracting microglia and monocytes and promoting their secretion of CCL2 in the injured position.

Generation and characterization of immortalized rat retinal microglial cell lines.

Retinal microglia play an important role as resident immunocompetent and phagocytic cells in the event of injury and disease. Retinal microglia and microglia precursor transplantation show a rescue effect in ischemic retina and retinal degeneration. However, studies of retinal microglia have been hampered by the difficulty of obtaining sufficient numbers of microglia. One way to circumvent this difficulty is to establish permanent retinal microglia cell lines. In the present study, we report the generation of immortalized retinal microglia, T-MG cells, from postnatal day 3 rat retinal tissue using a lentiviral vector encoding SV40 large T antigen. The T-MG cells exhibited cell-type-specific antigens for monocyte/macrophage lineage cells, including CD11b (OX42), ED1 (OX6), and Iba1, and actively phagocytosed latex beads. In addition to primary retinal microglia, T-MG cells also have the ability to recruit into chemokines. Treatment of T-MG cells with lipopolysaccharide (LPS) led to increased levels of tumor necrosis factor-α, interleukin-1ß, and inducible nitric oxide synthase. Genome-wide microarray analysis showed a less than 1% difference in the genes between the T-MG cells and the control primary retinal microglia. The T-MG cells exhibited properties similar to those of the primary retinal microglia and should have considerable utility as an in vitro model for the study of retinal microglia in health and as a curative therapy and an in vivo model for the study of retinal microglia in disease.

CCR2 overexpression promotes the efficient recruitment of retinal microglia in vitro.

PURPOSE: Retinal microglia can be activated and recruited by chemokines and play a protective role in early retinal degeneration. CC-chemokine ligand 2 (CCL2) and its receptor, CC-chemokine receptor 2 (CCR2), have been implicated as key mediators for the trafficking and accumulation of microglial cells in lesioned tissue. The current study investigates whether the overexpression of CCR2 allows microglia to migrate toward CCL2 more efficiently. METHODS: Primary microglial cells were transduced with lentivirus carrying green fluorescent protein (GFP)-tagged CCR2 (CCR2-GFP). Overexpression of CCR2 was assessed by western blot analysis and fluorescence-assisted cell sorting. The chemotaxis of primary microglia transduced with lentivirus carrying CCR2-GFP was compared to either those transduced with GFP alone or those not transduced, using a chemotaxis chamber assay. RESULTS: Primary microglia showed a high transduction rate following lentivirus application and maintained normal microglial morphology and a significant overexpression of CCR2 protein. We found that CCL2-mediated chemotaxis is concentration and time dependent in microglia. The chemotactic response of microglia cells overexpressing CCR2-GFP was significantly increased compared to that of nontransduced and GFP-expressing microglia. CONCLUSIONS: These findings suggest that microglia can be efficiently transduced with CCR2-GFP lentiviral vectors and that the overexpression of CCR2 in retinal microglia promotes their chemotaxis in response to chemokines, suggesting that these cells may be promising targets for cell-based therapeutic manipulation in retinal disease.

Resolution of Harada disease-like uveitis after quadrivalent human papillomavirus vaccination: a case report.

This article describes a patient who developed Harada disease-like uveitis after quadrivalent human papillomavirus (HPV4) vaccination and experienced resolution without any systemic treatment. To achieve this aim, a case report and a review of related literature on HPV vaccination causing uveitis were conducted. The results of this study show a diagnosis of Harada disease-like uveitis after HPV4 vaccination based on the vaccination history, clinical symptoms, and multimodal imaging. Resolution without any systemic corticosteroid treatment was observed. According to these findings, patients may develop uveitis with Harada-like features, which can be a mild and self-limiting process, after HPV4 vaccination.

Metamorphopsia and Morphological Changes in the Macula after Scleral Buckling Surgery for Macula-Off Rhegmatogenous Retinal Detachment.

PURPOSE: To observe the changes in metamorphopsia after scleral buckling (SB) surgery for macula-off rhegmatogenous retinal detachment (RRD) and its association with morphological changes in the macula. METHODS: This prospective study included 20 eyes of 20 patients. Before surgery and 1, 3, 6, and 12 months after surgery, metamorphopsia measured by M-charts and best-corrected visual acuity (BCVA) and macular microstructures assessed using optical coherence tomography were recorded. RESULTS: Both the vertical and horizontal M-scores improved significantly after SB surgery. BCVA also improved gradually. The mean M-score in the eyes with a continuous external limiting membrane (ELM) was smaller than that in the eyes with a disrupted ELM (P=0.008). Preoperative and postoperative BCVA did not correlate with the mean M-score at any time point. The other studied parameters, namely, the duration of RRD, the height of retinal detachment, central foveal thickness, inner nuclear layer thickness, and continuation of the ellipsoid zone, were also not relevant. CONCLUSIONS: The continuation of the ELM may be a critical factor in determining the severity of metamorphopsia after SB surgery for macula-off RRD.

Optimised retinopathy of prematurity screening guideline in China based on a 5-year cohort study.

PURPOSES: To develop an optimised retinopathy of prematurity (ROP) screening guideline by adjusting the screening schedule and thresholds of gestational age (GA) and birth weight (BW). METHODS: A multicentre retrospective cohort study was conducted based on data from four tertiary neonatal intensive care units in Shanghai, China. The medical records of enrolled infants, born from 2012 to 2016 who underwent ROP examinations, were collected and analysed. The incidence and risk factors for ROP were analysed in all infants. Postnatal age (PNA) and postmenstrual age (PMA) of infants, detected to diagnose ROP for the first time, were compared with the present examination schedule. The predictive performance of screening models was evaluated by internally validating sensitivity and specificity. RESULTS: Of the 5606 eligible infants, ROP was diagnosed in 892 (15.9%) infants; 63 (1.1%) of them received treatment. The mean GA of ROP patients was 29.4±2.4 weeks, and the mean BW was 1260±330 g. Greater prematurity was associated with an older PNA at which ROP developed. The minimum PMA and PNA at which diagnosis of treatable ROP occurred were 32.43 and 3 weeks, respectively. The optimised criteria (GA <32 weeks or BW <1600 g) correctly predicted 98.4% type 1 ROP infants, reducing the infants requiring examinations by 43.2% when internally validated. CONCLUSIONS: The incidence of type 1 ROP and the mean GA and BW of ROP infants have decreased in China. The suggested screening threshold and schedule may be reliably used to guide the modification of ROP screening guideline and decrease medical costs.

Progression Patterns of Myopic Traction Maculopathy in the Fellow Eye After Pars Plana Vitrectomy of the Primary Eye.

Purpose: This retrospective study investigated the patterns and risk factors of progression of myopic traction maculopathy (MTM) of fellow eyes after pars plana vitrectomy (PPV) of primary eyes. Methods: The study population comprised 153 patients with MTM in both myopic eyes who sequentially underwent PPV (2006-2021). Observation periods were from PPV of the primary eye (baseline) to PPV of the fellow (end). MTM was graded based on optical coherence tomography (OCT) images and the ATN (atrophy [A], traction [T], and neovascularization [N]) system. An increase in T grade was considered MTM progression. Results: MTM progressed in 43.8% of fellow eyes during 34.57 ± 34.08 months. The progression of fellow eyes correlated with T grade of primary eyes (P < 0.001). Risk factors for the progression of MTM in fellow eyes were primary eyes in T4-T5, age at baseline <60 years, and fellow eyes with partial posterior vitreous detachment (PVD; P < 0.001, P = 0.042, and P = 0.002, respectively). Fellow eyes in T1/T2 at baseline progressed faster compared with those in T0 (P < 0.001); the annual rate of progression to T3-T5 of the T0 (T1-T2) groups was 9.98% (24.59%). Conclusions: Risk factors for the progression of MTM in fellow eyes included PPV when relatively young, primary eye at high T grade, and partial PVD of the fellow eye. Personalized follow-up for fellow eyes should be based on the severity of MTM of both eyes.

Clinical features and changes of disease spectrum of zone II retinopathy of prematurity: a 10-year review.

AIM: To report the clinical features and evolution of zone II retinopathy of prematurity (ROP). METHODS: RetCam images of preterm infants with zone II ROP at our hospital between January 2009 and January 2019 were reviewed. The location, extent, and severity of ROP were recorded. Eyes were classified as type 1 zone II, type 2 zone II, and mild zone II ROP. The clinical features and evolution of zone II ROP were analyzed. RESULTS: In total, 184 infants (302 eyes) were enrolled. Of these, 55 eyes (18%) developed type 1 zone II ROP, 39 eyes (13%) developed type 2 zone II ROP, and 208 eyes (69%) developed mild zone II ROP. The proportion of type 1 zone II ROP significantly decreased over the 10y. The onset of type 2 zone II and mild zone II ROP were 1wk earlier than type 1 zone II, and both regressed at 45wk. Isolated neovascular tuft (popcorn) and double track signs were characteristic manifestations of zone II ROP. Eighty-seven percent of type 1 zone II ROP regressed completely with an unfavorable outcome that emerged in seven eyes after laser treatment. CONCLUSION: Zone II is an area with ROP disease at various risk levels. Zone II ROP has unique clinical presentations like popcorn and double track signs. Over time, the proportion of zone II ROP with high risk gradually decrease and respond well to therapy.

Rate and Treatment of Retinopathy of Prematurity in Extremely Low Birth Weight Infants with Gestational Age ≤28 Weeks in Eastern China.

PURPOSE: To investigate the incidence and clinical characteristics of ROP in extremely preterm (EP) and extremely low birth weight (ELBW) infants in eastern China. PATIENTS AND METHODS: This retrospective study included 104 infants with a birth weight (BW) ≤ 1000 g and gestational age (GA) ≤ 28 weeks, who were admitted to the Eye and ENT Hospital of Fudan University over 10 years. The infants were examined for ROP with RetCam. Infants with type 1 ROP and aggressive posterior ROP (AP-ROP) were treated. The risk factors evaluated were GA and BW. RESULTS: Mean GA was 26.63 ± 0.88 weeks and mean BW was 892.39 ± 108.06 g. Of the 104 infants, 83 (79.8%) developed ROP, three (2.9%) had AP-ROP, 14 (13.5%) had type 1 ROP, and 10 (9.6%) had type 2 ROP. The proportions of infants with BW ≤750 g and 751-1000 g were 8.7% and 91.3%, respectively, and the incidences of severe ROP in these infants were 22.2% and 15.8%, respectively. The infants with severe ROP had a mean GA of 26.56 ± 0.68 weeks and mean BW of 860.00 ± 163.48 g, and 47.1% of severe ROP occurred in infants with a GA of 26 weeks. However, multivariate logistic regression showed that the severity of ROP was not directly inversely related to GA or BW in this study population. CONCLUSION: In EP and ELBW Chinese infants, who were admitted to the Eye and ENT Hospital of Fudan University, the development of ROP was more frequent and the incidence of severe ROP that progressed to the stage that required treatment was high.

Diagnostic Performance of MALDI-TOF MS Compared to Conventional Microbiological Cultures in Patients with Suspected Endophthalmitis.

Purpose: To evaluate the performance and speed of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) when identifying the pathogenic microorganism of endophthalmitis compared to conventional microbiological culturing.Methods: Forty-four patients with suspected endophthalmitis who had undergone vitrectomy were enrolled. Vitreous specimen was analyzed using either conventional culturing or MALDI-TOF MS.Results: The identification rates of the conventional microbiological culture and MALDI-TOF MS were 45.5% (20/44) and 65.9% (29/44), respectively (Kappa value 0.787, P < 0.000). The mean detection times by the standard culturing method and MALDI-TOF MS were 5.39 ± 0.56d and 3.17 ± 0.40d (P < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MALDI-TOF MS were 70.59%, 54.17%, 80.00%, and 86.67%, respectively. Polymicrobial endophthalmitis was identified in 6.82% of the patients (3/44) using conventional microbiological culturing. However, MALDI-TOF MS failed to identify any polymicrobial infection.Conclusions: With a higher sensitivity, acceptable specificity and a shorter detection time, MALDI-TOF MS was an efficient technique for the rapid identification of a pathogenic microorganism in endophthalmitis.

Neuroprotective effects of naloxone against light-induced photoreceptor degeneration through inhibiting retinal microglial activation.

PURPOSE: To determine the role of microglial activation in light-induced photoreceptor degeneration and the neuroprotective effects of naloxone as a novel microglial inhibitor. METHODS: Sprague-Dawley rats were exposed to intense blue light for 24 hours. Daily intraperitoneal injection of naloxone or PBS as a control was given 2 days before exposure to light and was continued for 2 weeks. Apoptotic cells were detected by the TUNEL assay, and anti-OX42 antibody was used to label retinal microglia. Western blot was applied to evaluate the retinal interleukin (IL)-1beta protein levels. Retinal histologic examination and electroretinography (ERG) were also performed to evaluate the effects of naloxone on light-induced photoreceptor degeneration. RESULTS: TUNEL-positive cells were noted in the outer nuclear layer (ONL) of the retina as early as 2 hours and peaked at 24 hours after exposure to light. OX42-positive microglia occurred in the ONL and subretinal space at 6 hours, peaked at 3 days, and changed morphologically from the resting ramified to the activated amoeboid. Expression of IL-1beta protein was also significantly increased at 3 days. Compared with the control, the number of microglia in the outer retina was significantly decreased in the naloxone-treated group at 3 days, and the thickness of ONL and the amplitudes of dark-adapted a- and b-waves were also well preserved at 14 days. CONCLUSIONS: The activation and migration of microglia and the expression of neurotoxic factor (IL-1beta) coincide with photoreceptor apoptosis, suggesting that activated microglia play a major role in light-induced photoreceptor degeneration. Inhibiting microglial activation by naloxone significantly reduces this degeneration.

CRISPR-mediated SOX9 knockout inhibits GFAP expression in retinal glial (Müller) cells.

Müller cells, as the predominant glial element in the sensory retina, play a crucial role in healthy and diseased retina. Overactivation of Müller cells in response to damage is detrimental to the retina tissue. Current research shows that inhibiting glial fibrillary acidic protein (GFAP), a sensitive indicator of Müller cell activation, attenuated glial reactions and promoted neuroprotection. Recent evidence suggests that the transcript factor SOX9 (sex-determining region Y box 9), part of the SOX family, regulates GFAP expression of astrocytes in the central nervous system. However, in retina Müller cells, it is still unknown whether GFAP can be downregulated by reduced SOX9 function. The present results show that clustered regularly interspaced short palindromic repeats/Cas9-mediated SOX9 knockout not only inhibited GFAP expression in rat Müller cells but also attenuated cell migration ability. These results suggest that inhibition of SOX9 activity may be a novel therapeutic strategy for reduction of glial cell activity.

Intravitreal injection of ranibizumab in severe retinopathy of incontinentia pigmenti.

Incontinentia pigmenti (IP) is a rare X-linked multisystem disorder that mainly affects females and is usually lethal to males in utero. Mutations in the NEMO gene on chromosome Xq28 (IKBKG, inhibitor of kB kinase gamma) have been shown to cause IP. Approximately 35% of patients have ophthalmic manifestations, and 20% develop vision-threatening diseases. Retinal vascular abnormalities, from peripheral retinal avascularity to neovascular proliferation, have been described in IP patients. Laser photocoagulation and cryotherapy are traditionally effective therapy for retinopathy of IP. However, some cases still progress to retinal detachment. We report 2 cases of IP infants treated with intravitreal ranibizumab with subsequent resolution of the vasculopathy.

Pediatric Infectious Endophthalmitis: A 271-case Retrospective Study at a Single Center in China.

BACKGROUND: Pediatric infectious endophthalmitis is a serious sight-threatening disease for children. The purpose of this study was to investigate the etiology, microbiological spectrum, and visual outcomes of infectious endophthalmitis in children at a single institution in China. METHODS: It is a retrospective study of the medical records of all patients under 14 years of age with histories of infectious endophthalmitis, treated at a single institution from January 1, 2009 to January 1, 2015. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. The Kappa test and Chi-square test were used in the statistical evaluation. RESULTS: A total of 271 children were identified, with a mean age of 5.61 ± 2.93 years (range 5 months to 14 years). Ocular trauma (94.8%) and previous ocular surgery (3.0%) were the most common etiologies. Overall, 147 (54.2%) cases had positive cultures, and 176 organisms were isolated from these patients. A single species was isolated in 120 (81.6%) cases, with multiple organisms in 27 (18.4%) cases, and the most commonly identified organisms were coagulase-negative Staphylococcus and Streptococcus species, comprising 29.5% and 26.8% of the isolates, respectively. Moreover, of 176 isolates, 142 (80.8%) were Gram-positive organisms, 23 (13.0%) were Gram-negative organisms, and 11 (6.2%) were fungi. The final visual outcomes were 20/200 or better in 66 (24.4%) eyes, counting fingers to 20/200 in 34 (12.5%), hand motions in 30 (11.1%), light perception in 33 (12.2%), no light perception in 32 (11.8%), and 9 (3.3%) eyes were enucleated or eviscerated. The visual outcomes were not available in 67 (24.7%) patients. CONCLUSIONS: Penetrating ocular trauma is the most frequent cause of pediatric endophthalmitis in China. Streptococcus and Staphylococcus species are the most commonly identified organisms in exogenous pediatric endophthalmitis whereas Fusarium species are commonly seen in endogenous endophthalmitis. In this research, in spite of aggressive management with antibiotics and vitrectomy, the visual prognosis was found to be generally poor.