Therapeutic potential of histamine H4 receptor antagonist as a preventive treatment for diabetic retinopathy in mice.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, often resulting in vision loss and blindness. Existing treatments primarily aim to control blood sugar levels and inhibit angiogenesis. However, current therapies for DR, such as anti-VEGF and laser photocoagulation, are frequently invasive, and can cause adverse side effects. Consequently, there is a critical need for new preventive therapeutics to address DR more effectively. This study aimed to examine the therapeutic potential of a histamine H4 receptor (HRH4) antagonist as a preventive treatment for DR in mice. A mouse model of DR was established by intraperitoneally injecting 200 mg/kg of streptozotocin (STZ). Immune cell infiltration into the retina of mice with STZ-induced diabetes was measured using fluorescence-activated cell sorting (FACS) 12 weeks after STZ injection. The preventive effects of the HRH4 antagonist on inflammation and pathological retinal vessel leakage were determined in a mouse model of DR. Infiltration of HRH4-expressing macrophages increased in the retina of mice with STZ-induced DR. The HRH4 antagonist prevented macrophage infiltration and retinal vascular leakage to prevent STZ-induced DR in mice without causing any retinal toxicity. The infiltration of macrophages increased in the retina of mice with STZ-induced diabetes through HRH4, indicating that HRH4 is potentially a novel preventative therapeutic target in DR. These findings suggest that targeting HRH4 is a promising strategy for the prevention and treatment of DR.

Chlorogenic acid ameliorates non-proliferative diabetic retinopathy via alleviating retinal inflammation through targeting TNFR1 in retinal endothelial cells.

As a prominent complication of diabetes mellitus (DM) affecting microvasculature, diabetic retinopathy (DR) originates from blood-retinal barrier (BRB) damage. Natural polyphenolic compound chlorogenic acid (CGA) has already been reported to alleviate DR. This study delves into the concrete mechanism of the CGA-supplied protection against DR and elucidates its key target in retinal endothelial cells. DM in mice was induced using streptozotocin (STZ). CGA mitigated BRB dysfunction, leukocytes adhesion and the formation of acellular vessels in vivo. CGA suppressed retinal inflammation and the release of tumor necrosis factor-α (TNFα) by inhibiting nuclear factor kappa-B (NFκB). Furthermore, CGA reduced the TNFα-initiated adhesion of peripheral blood mononuclear cell (PBMC) to human retinal endothelial cell (HREC). CGA obviously decreased the TNFα-upregulated expression of vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1), and abrogated the TNFα-induced NFκB activation in HRECs. All these phenomena were reversed by overexpressing type 1 TNF receptor (TNFR1) in HRECs. The CGA-provided improvement on leukocytes adhesion and retinal inflammation was disappeared in mice injected with an endothelial-specific TNFR1 overexpression adeno-associated virus (AAV). CGA reduced the interaction between TNFα and TNFR1 through binding to TNFR1 in retinal endothelial cells. In summary, excepting reducing TNFα expression via inhibiting retinal inflammation, CGA also reduced the adhesion of leukocytes to retinal vessels through decreasing VCAM1 and ICAM1 expression via blocking the TNFα-initiated NFκB activation by targeting TNFR1 in retinal endothelial cells. All of those mitigated retinal inflammation, ultimately alleviating BRB breakdown in DR.

Dexamethasone intravitreal implant in the treatment of macular edema secondary to necrotizing retinitis.

PURPOSE: To describe our experience with the use of a sustained-release dexamethasone implant in three patients with recalcitrant macular edema that developed after necrotizing retinitis in the context of the previously treated virus. CASE DESCRIPTION: Two immunocompetent patients presented with unilateral acute retinal necrosis (ARN) due to Varicella-Zoster (VZV). The other, an immunocompromised patient, presented with unilateral cytomegalovirus (CMV) necrotizing retinitis. The diagnoses were confirmed by anterior chamber polymerase chain reaction (PCR) and all were treated with oral valganciclovir and intravitreal ganciclovir (2 mg/0.1 ml). Infection was controlled but two of them required pars plana vitrectomy. Between 2 and 4 months after the resolution of signs of infection, resistant macular edema (RME) developed, and an intravitreal dexamethasone device was implanted after anterior chamber PCR had been negative. Functional and anatomical improvement was achieved, with the resolution of the edema accompanied by improvement in visual acuity in all patients. There was no evidence of reactivation at two years. No cataract or ocular hypertension was observed. One patient required two additional dexamethasone implants. CONCLUSION: Dexamethasone intravitreal implant could be considered as an option for the treatment of macular edema developed after ARN. Care should be taken to avoid reactivation and patients need to be properly informed.

Lutein Modulates Cellular Functionalities and Regulates NLRP3 Inflammasome in a H2O2-Challenged Three-Dimensional Retinal Pigment Epithelium Model.

Excessive hydrogen peroxide (H2O2) generated during retinal cell metabolic activity could lead to oxidative degeneration of retinal pigment epithelium (RPE) tissue, a specific pathological process implicated in various retinal diseases resulting in blindness, which can be mitigated by taking dietary antioxidants to prevent inflammation and impaired cellular dysfunction. This study tested the hypothesis that damages induced by oxidative stresses can be mitigated by lutein in a H2O2-challenged model, which was based on an ARPE-19 cell monolayer cultured on three-dimensional (3D)-printed fibrous scaffolds. Pretreating these models with lutein (0.5 µM) for 24 h can significantly lower the oxidative stress and maintain phagocytosis and barrier function. Moreover, lutein can modulate the NLRP3 inflammasome, leading to a ∼40% decrease in the pro-inflammatory cytokine (IL-1ß and IL-18) levels. Collectively, this study suggests that the 3D RPE model is an effective tool to examine the capability of lutein to modulate cellular functionalities and regulate NLRP3 inflammation.

Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

Punctate Inner Choroidopathy (PIC) disease recurrence with inflammatory choroidal neovascular membrane (iCNVM) post-COVID-19 vaccine.

PURPOSE: To report a recurrence of punctate inner choroidopathy (PIC) with an inflammatory choroidal neovascular membrane (iCNVM) after the Pfizer-BioNTech COVID-19 vaccine. METHODS: Case report. RESULTS: A 38-year-old female with a history of myopia and previous episodes of PIC and iCNVM presented with distorted vision in her right eye, seven days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. The patient exhibited active PIC lesions with iCNVM confirmed on multimodal imaging. Treatment with a combination of oral corticosteroids and intravitreal anti-VEGF injection led to disease resolution. Subsequent COVID-19 vaccinations, administered while the patient was immunosuppressed, did not lead to disease relapse. However, relapse occurred following the fourth COVID-19 vaccine, when the patient was not immune suppressed. CONCLUSION: This case highlights the potential risk of PIC disease relapse following COVID-19 vaccination. Further research is needed to investigate the relationship between COVID-19 vaccination and PIC exacerbation, as well as to determine optimal management strategies in this population, including close observation and consideration of prophylactic immune suppression at the time of COVID-19 vaccine for high-risk individuals.

The Surprising Nonlinear Effects of S100A9 Proteins in the Retina.

Age-related macular degeneration (AMD) is a complex disease in which inflammation is implicated as a key factor but the precise molecular mechanisms are poorly understood. AMD lesions contain an excess of the pro-inflammatory S100A9 protein, but its retinal significance was yet unexplored. S100A9 was shown to be intrinsically amyloidogenic in vitro and in vivo. Here, we hypothesized that the retinal effects of S100A9 are related to its supramolecular conformation. ARPE-19 cultures were treated with native dimeric and fibrillar S100A9 preparations, and cell viability was determined. Wild-type rats were treated intravitreally with the S100A9 solutions in the right eye and with the vehicle in the left. Retinal function was assessed longitudinally by electroretinography (ERG), comparing the amplitudes and configurations for each intervention. Native S100A9 had no impact on cellular viability in vitro or on the retinal function in vivo. Despite dispersed intracellular uptake, fibrillar S100A9 did not decrease ARPE-19 cell viability. In contrast, S100A9 fibrils impaired retinal function in vivo following intravitreal injection in rats. Intriguingly, low-dose fibrillar S100A9 induced contrasting in vivo effects, significantly increasing the ERG responses, particularly over 14 days postinjection. The retinal effects of S100A9 were further characterized by glial and microglial cell activation. We provide the first indication for the retinal effects of S100A9, showing that its fibrils inflicted retinal dysfunction and glial activation in vivo, while low dose of the same assemblies resulted in an unpredicted enhancement of the ERG amplitudes. These nonlinear responses highlight the consequences of self-assembly of S100A9 and provide insight into its pathophysiological and possibly physiological roles in the retina.

Evaluation of retinal and choroidal vascular structures in patients with anxiety disorder.

PURPOSE: To evaluate the retinal and choroidal vascular structures in patients with anxiety disorders. METHODS: Thirthy-four eyes of 34 patients who were diagnosed with any anxiety disorders were compared with 32 eyes of 32 age- and sex-matched controls. Central macular thickness (CMT), foveal vascular zone (FAZ) area, total retinal vascular densities of superficial and deep capillary plexus (VDSCP, VDDCP), outer retinal and choriocapillary layers (ORL, CCL) blood flow rates, central subfoveal choroidal thickness (SFCT) and choriodal vascularity index (CVI) were evaluated with optical coherence tomography angiography (OCT-A) and enhanced depth imaging optical coherence tomography (EDI-OCT). RESULTS: No statistical differences were found between the study and control groups in terms of CMT, FAZ area, VDSCP, VDDCP, ORL and CCL blood flow rates. The mean SFCT was 346.26 ± 64.26 µm in patients with anxiety disorder and was found to be statistically significantly thicker than the control group (319.56 ± 37.19 µm) (p = 0.042). Besides, CVI was significantly lower in the study group (71.09 ± 2.64 vs 73.13 ± 3.31, p = 0.008). CONCLUSION: In people with anxiety disorders, the SFCT was found to be thicker and CVI was found to be lower than normal subjects. Although anxiety and stress are important factors in central serous chorioretinopathy, multifactorial factors, including ocular factors, play a role in the pathophysiology of the disease. There is a need for prospective studies with larger series on the subject.

Choroidal neovascularization and MEWDS like reaction in a child: A rare case.

PURPOSE: To report a case of choroidal neovascularization (CNV) associated with Multiple Evanescent White Dot Syndrome (MEWDS) in a child. STUDY DESIGN: Case report. RESULTS: A 13-year-old child visited us with a month-long history of blurred vision in his right eye. His right fundus showed several subretinal white dots and an atrophic macular lesion corresponding to a CNV. Angiography and optical coherence tomography (OCT) were consistent with the diagnosis of MEWDS. The patient's condition poorly improved after an intravitreal injection of anti-vascular endothelial growth factor (anti VEGF) in his right eye. CONCLUSIONS: We reported the case of CNV associated with MEWDS like reaction. The hypothesis of a triggered-MEWDS was highly suspected but no cause was found, which is often the case in paediatric inflammatory eye disorders. Long-term follow-up is needed to judge the evolution.

A morphometric analysis of the retinal arterioles with adaptive optics imaging in RPE65-associated retinal dystrophy after treatment with voretigene neparvovec.

PURPOSE: To investigate the changes in retinal arterial architecture after treatment with voretigene neparvovec in patients with retinal dystrophy caused by bi-allelic mutations in the RPE65 gene. METHODS: Sixteen eyes treated with voretigene neparvovec at the University Eye Clinic in Tuebingen, Germany, underwent adaptive optics ophthalmoscopy (AO) imaging at baseline and 2 weeks, 1, 3, 6 and 12 months after treatment. Follow-up was performed in six eyes of four patients. For each eye, five different positions at arterial vessels were selected and the wall-to-lumen ratio (WLR), the lumen diameter (LD) and the wall cross-sectional area (WCSA) were measured by the manufacturer's software over the observational period. RESULTS: Vast retinal atrophy dominated all gained AO images. WLR fluctuated in the observation period without statistically significant change. LD and WCSA changed significantly after 2 weeks from the baseline examination and returned to values similar to baseline thereafter. There were no signs of inflammation such as macrophages or perivascular accumulated fluid visible. CONCLUSION: AO imaging of the retinal vessels in RPE65-associated retinal dystrophies (IRD) is challenging. There was no change in the retinal arterial vasculature over the observation period of 12 months that would indicate inflammatory changes. Decrease of the LD and WCSA shortly after treatment might be caused by the perioperative prednisolone intake. AO of retinal vessels can be used as a diagnostic module to complement monitoring the disease and effects of genetic treatments if the acquisition is possible in selected cases.

Unilateral solitary choroidal tuberculoma as the presenting sign in disseminated tuberculosis in an immunocompetent patient.

INTRODUCTION: Tuberculosis can involve any organ in the body including ocular tissue of which the uveal tissue is most commonly infected. Choroidal involvement ranges from choroidal tubercles to granulomas. This is one of the few cases of a solitary choroidal granuloma with no other systemic symptoms in an immunocompetent child. METHOD: A case report. RESULTS: A 12-year-old female, presented with diminution of vision in the left eye for a month. The anterior segment of her left eye was normal. A fundus examination revealed an isolated orangish-yellow choroidal mass, 4 DD in size, involving the posterior pole with overlying subretinal exudation. CT scan of the thorax showed large pulmonary, cervical and pancreatic lymph nodes, along with lytic lesions of the thoracic vertebrae. Excision biopsy of the cervical lymph nodes showed caseating granulomas with no e/o malignancies on histopathology. The patient was started on anti-tubercular therapy. Six months after the treatment, the lesion had reduced in size and her vision had improved. CONCLUSION: Isolated choroidal tuberculomas can be present in eyes with little associated ocular inflammation and no other symptoms of systemic tuberculosis. High suspicion, early diagnosis and rapid initiation of medication are important for the treatment of ocular and systemic tuberculosis.

Pharmacological Modulation of ß-Catenin Preserves Endothelial Barrier Integrity and Mitigates Retinal Vascular Permeability and Inflammation.

Compromised blood-retinal barrier (BRB) integrity is a significant factor in ocular diseases like uveitis and retinopathies, leading to pathological vascular permeability and retinal edema. Adherens and tight junction (AJ and TJ) dysregulation due to retinal inflammation plays a pivotal role in BRB disruption. We investigated the potential of ICG001, which inhibits ß-catenin-mediated transcription, in stabilizing cell junctions and preventing BRB leakage. In vitro studies using human retinal endothelial cells (HRECs) showed that ICG001 treatment improved ß-Catenin distribution within AJs post lipopolysaccharide (LPS) treatment and enhanced monolayer barrier resistance. The in vivo experiments involved a mouse model of LPS-induced ocular inflammation. LPS treatment resulted in increased albumin leakage from retinal vessels, elevated vascular endothelial growth factor (VEGF) and Plasmalemmal Vesicle-Associated Protein (PLVAP) expression, as well as microglia and macroglia activation. ICG001 treatment (i.p.) effectively mitigated albumin leakage, reduced VEGF and PLVAP expression, and reduced the number of activated microglia/macrophages. Furthermore, ICG001 treatment suppressed the surge in inflammatory cytokine synthesis induced by LPS. These findings highlight the potential of interventions targeting ß-Catenin to enhance cell junction stability and improve compromised barrier integrity in various ocular inflammatory diseases, offering hope for better management and treatment options.

Long-lived autoreactive memory CD4+ T cells mediate the sustained retinopathy in chronic autoimmune uveitis.

Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis. We demonstrate unique long-lived CD44hi IL-7R+ IL-15R+ CD4+ memory T cells in both retina and secondary lymphoid organs after 3 months postinduction of autoimmune uveitis. These memory T cells functionally exhibit antigen-specific proliferation and activation in response to retinal peptide stimulation in vitro. Critically, these effector-memory T cells are capable of effectively trafficking to the retina and accumulating in the local tissues secreting both IL-17 and IFN-γ upon adoptively transferred, leading to retinal structural and functional damage. Thus, our data reveal the critical uveitogenic functions of memory CD4+ T cells in sustaining chronic intraocular inflammation, suggesting that memory T cells can be a novel and promising therapeutic target for treating chronic uveitis in future translational studies.

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.

Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during retinal development. In certain retinal diseases, the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea). Furthermore, continuously activated microglia secrete inflammatory factors and expedite the loss of the blood-retinal barrier which causes irreversible damage to the secondary death of neurons. In this review, we support microglia can be a potential cellular therapeutic target in retinopathy. We briefly describe the relevance of microglia to the retinal vasculature and blood-retinal barrier. Then we discuss the signaling pathway related to how microglia move to their destinations and regulate vascular regeneration. We summarize the properties of microglia in different retinal disease models and propose that reducing the number of pro-inflammatory microglial death and conversing microglial phenotypes from pro-inflammatory to anti-inflammatory are feasible for treating retinal neovascularization and the damaged blood-retinal barrier (BRB). Finally, we suppose that the unique properties of microglia may aid in the vascularization of retinal organoids.

Recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination.

PURPOSE: To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year. METHODS: Retrospective observational case reports. RESULTS: Two patients (one female and one male) under follow-up for posterior uveitis having stable course with absence of ocular inflammation for more than a year presented with recurrence of choroiditis lesions 2-6 weeks following anti-SARS-CoV-2 vaccination. Both the patients were managed with intravitreal dexamethasone implant (Ozurdex®, Allergan, Inc., Irvine, CA, USA) and showed resolution of choroiditis lesions upon follow-up. CONCLUSIONS: Acute onset recurrence of inflammation, in absence of any change in health status or treatment suggests the potential role of vaccination being the trigger of this reactivation. Given large-scale vaccination against novel coronavirus- SARS-CoV-2, careful vigilance is warranted to pick up the disease recurrence in patients with posterior uveitis.

Retinal microvascular abnormalities, cotton wool-like lesions, and macular edema following COVID-19 in a patient previously vaccinated with AstraZeneca and idiopathic myopathy.

In this case study, the authors describe peculiar bilateral cotton wool-like retinal lesions associated with macular edema in a patient with COVID-19 who was vaccinated with a single dose of AstraZeneca one month earlier. This patient had no pulmonary or systemic cardiovascular complications from COVID-19, as reported in other papers that found retinal lesions. However, the patient was diagnosed with idiopathic myopathy when discovering the SARS-CoV-2 infection. The patient was a 22-year-old white female with no previous history of morbidity, complaining of blurred vision in both eyes seven days after testing positive for SARS-CoV-2 by PCR (using nasal and oral swab) and confirmed through ELISA blood test (IgM positive). There was no ancillary test revealing diabetes mellitus. The patient presented with scattered whitish cotton wool-like lesions and a few hemorrhages on the posterior pole in fundus examination. On spectral domain optical coherence tomography (SD-OCT), there were hyperreflective lesions in the nerve fiber layer, ganglion cell layer, inner nuclear layer, and inner and outer plexiform layers at the site corresponding to the whitish cotton wool-like lesions in the posterior fundus photos. Moreover, the macula of both eyes had intraretinal and subretinal fluid, reversible with corticosteroid therapy. In conclusion, COVID-19 has been associated with capillary disorders at different target sites such as retina, lungs, and central nervous system. Similarly, vaccination against SARS-CoV-2 has been linked to retinal complications in the literature; however, cotton wool-like lesions have not yet been reported. There are many questions yet to be answered about the implications of COVID-19 infection and its vaccines.

Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.

Retinitis pigmentosa (RP) is an important cause of irreversible blindness worldwide and lacks effective treatment strategies. Although mutations are the primary cause of RP, research over the past decades has shown that neuroinflammation is an important cause of RP progression. Due to the abnormal activation of immunity, continuous sterile inflammation results in neuron loss and structural destruction. Therapies targeting inflammation have shown their potential to attenuate photoreceptor degeneration in preclinical models. Regardless of variations in genetic background, inflammatory modulation is emerging as an important role in the treatment of RP. We summarize the evidence for the role of inflammation in RP and mention therapeutic strategies where available, focusing on the modulation of innate immune signals, including TNFα signaling, TLR signaling, NLRP3 inflammasome activation, chemokine signaling and JAK/STAT signaling. In addition, we describe epigenetic regulation, the gut microbiome and herbal agents as prospective treatment strategies for RP in recent advances.

Reply to letter to editor.

We aimed to explain the questions about choroidal vascularity index (CVI) calculation which mentioned in the manuscript entitled 'Acute effects of coffee on peripapillary and subfoveal choroidal parameters in young healthy subjects'.

Cuscuta chinensis Lam. Protects Against Light-Induced Retinal Degeneration: Therapeutic Implications for Photoreceptor Degenerative Disorders.

Cuscuta chinensis Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases.

Regulations of Retinal Inflammation: Focusing on Müller Glia.

Retinal inflammation underlies multiple prevalent retinal diseases. While microglia are one of the most studied cell types regarding retinal inflammation, growing evidence shows that Müller glia play critical roles in the regulation of retinal inflammation. Müller glia express various receptors for cytokines and release cytokines to regulate inflammation. Müller glia are part of the blood-retinal barrier and interact with microglia in the inflammatory responses. The unique metabolic features of Müller glia in the retina makes them vital for retinal homeostasis maintenance, regulating retinal inflammation by lipid metabolism, purine metabolism, iron metabolism, trophic factors, and antioxidants. miRNAs in Müller glia regulate inflammatory responses via different mechanisms and potentially regulate retinal regeneration. Novel therapies are explored targeting Müller glia for inflammatory retinal diseases treatment. Here we review new findings regarding the roles of Müller glia in retinal inflammation and discuss the related novel therapies for retinal diseases.