Optical coherence tomography (OCT) is an advanced retinal imaging technique that enables non-invasive cross-sectional visualization of the retina, playing a crucial role in ophthalmology for detecting various macular lesions. While deep learning has shown promise in OCT image analysis, existing studies have primarily focused on broad, image-level disease diagnosis. This study introduces the Assistive Diagnosis Framework for OCT (ADF-OCT), which utilizes a dataset of over one million macular OCT images to construct a multi-label diagnostic model for common macular lesions and a medical report generation module. Our innovative Multi-frame Medical Images Distillation method effectively translates study-level multi-label annotations into image-level annotations, thereby enhancing diagnostic performance without additional annotation information. This approach significantly improves diagnostic accuracy for multi-label classification, achieving an impressive AUROC of 0.9891 with best performance macro F1 of 0.8533 and accuracy of 0.9411. By refining the feature fusion strategy in multi-frame medical imaging, our framework substantially enhances the generation of medical reports for OCT B-scans, surpassing current solutions. This research presents an advanced development pipeline that utilizes existing clinical datasets to provide more accurate and comprehensive artificial intelligence-assisted diagnoses for macular OCT.

IntroductionUveitis, a severe inflammatory disease affecting the uvea, is associated with visual impairment and irreversible blindness. Asperulosidic Acid (ASPA), derived from Hedyotis diffusa, is known for its notable anti-inflammatory and antioxidant characteristics.MethodsThe present study explored the potential anti-inflammatory effects and the fundamental processes of ASPA by injecting it or a placebo into the vitreous of rats with endotoxin-induced uveitis (EIU). The severity of the disease was assessed using clinical scores obtained through slit lamp examination. The study involved the examination of protein concentrations and cell count in the aqueous humor (AqH), the detection of inflammatory mediators expressed in the retina. We evaluated the expression levels of various proteins, including the tight junction protein ZO-1, the endothelial marker VE-cadherin, and the key inflammatory mediators NF-κB and its phosphorylated form, along with the regulatory proteins IκB-a and IKK in their phosphorylated and non-phosphorylated states.ResultsASPA treatment significantly reduced the clinical score of EIU, including inflammatory leukocyte penetration, protein accumulation, cellulose-like exudates, the expression of ICAM-1, IL-6, MCP-1, and TNF-α in the AqH; and adhesion of leukocytes. The activation of the PI3K/Akt/NF-κB pathway was observed in EIU. Nevertheless, pretreatment with ASPA significantly suppressed the release of ICAM-1, TNF-α, MCP-1, and IL-6.DiscussionASPA may play a role in suppressing LPS-induced inflammation by obstructing the activation of the PI3K/Akt/NF-κB signaling pathway. As a result, ASPA has shown the capacity to significantly reduce immune inflammation.

PurposeTo compare the efficacy of intravitreal antivascular endothelial growth factor (anti-VEGF) agents with oral carbonic anhydrase inhibitors (CAIs) in treating cystoid macular edema (CME) secondary to retinitis pigmentosa (RP).MethodsThis retrospective study analyzed 98 patients (98 eyes) with RP-CME: 47 (48.0%) received intravitreal anti-VEGF agents (Ranibizumab or Bevacizumab) and 51 (52.0%) were treated with oral CAIs (methazolamide 50 mg/day or acetazolamide 500 mg/day). Medical records were reviewed to assess best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) at baseline and at 1, 3, 6, and 12 months post-treatment using Generalized Estimation Equations (GEE). Adverse events and risk factors influencing visual prognosis were also evaluated.ResultsBoth groups showed significant improvement in BCVA and reduction in CMT at 1 and 3 months post-treatment compared to baseline (all p < 0.001). In the oral CAIs group, these improvements persisted until 6 months. However, by 12 months, neither group exhibited significant improvements in BCVA or CMT compared to baseline (all p > 0.05). Intragroup comparisons revealed that the oral CAIs group had significantly better BCVA and CMT improvements at 3 and 6 months than intravitreal anti-VEGF group (p < 0.001 for BCVA at 3 months, p = 0.003 for BCVA at 6 months; all p < 0.001 for CMT at both 3 and 6 months). No significant differences were found between the two groups in BCVA and CMT at 12 months or in IOP at any time point (all p > 0.05). Subgroup analysis indicated that oral acetazolamide was more effective than methazolamide in reducing CMT and improving BCVA at 3 and 6 months (p = 0.005 for BCVA at 3 months, p = 0.015 for BCVA at 6 months; p = 0.037 for CMT at 3 months, p < 0.001 for CMT at 6 months). There were no significant differences in outcomes between intravitreal Ranibizumab and Bevacizumab (all p > 0.05). Correlation analysis showed that worse BCVA at 12 months was associated with older age (r = 0.202, p = 0.046), higher baseline CMT (r = 0.353, p < 0.001), poorer baseline BCVA (r = 0.579, p < 0.001), but showed no correlation with genotype. Adverse effects from oral CAIs included tingling sensation (3.9%), altered taste (9.8%), and gastrointestinal upset (7.8%). The Ranibizumab group required an average of 3.7 ± 0.8 treatments, and the Bevacizumab group required an average of 3.8 ± 0.5 treatments over the course of 1 year without experiencing severe adverse effects.ConclusionBoth intravitreal anti-VEGF agents and oral CAIs effectively improved CMT and BCVA in RP-CME patients within the first 3 months of treatment. However, oral CAIs demonstrated superior anatomic and functional improvements at 6 months. Poorer BCVA prognosis was associated with older age, higher baseline CMT, poorer baseline visual acuity. Larger, randomized clinical trials with extended follow-up periods are needed to confirm these findings.

PURPOSE:To assess the cone photoreceptors' morphology and associated retinal sensitivity in laser-induced retinopathy (LIR) using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and microperimetry (MP). DESIGN:Cohort study. METHODS:This study included 13 patients (15 eyes) with LIR and 38 age-matched healthy volunteers (38 eyes). Participants underwent comprehensive evaluations including AO-SLO, MP, and spectral-domain OCT. Lesion morphology, cone density, dispersion, and regularity in AO-SLO were assessed and correlated with visual function. RESULTS:In AO-SLO images, LIR lesions were predominantly characterized by hyporeflective regions, suggesting potential cone loss at the fovea, accompanied by the presence of sizable clumps of hyperreflective material within these lesions. The average size of lesions in affected eyes was 97,128±107,478 µm², ranging from 6705 to 673,348 µm². Compared with the healthy contralateral eye and control group, LIR demonstrated significantly reduced cone density, increased cone dispersion, and notably decreased cone regularity in all 4 quadrants at 3° eccentricity (all P values < .05). Lesion morphology in AO-SLO correlated with ellipsoid zone defects observed in OCT, showing a positive correlation in size (r = 0.84, P < .001) but not with retinal sensitivities (P = .09). Similarly, cone density at 3° eccentricity did not correlate with retinal sensitivities (P = .13). CONCLUSIONS AND RELEVANCE:The study provides crucial insights into the morphologic and functional impacts of LIR on cone photoreceptors, revealing significant morphologic changes in cones that do not consistently align with functional outcomes. This research highlights the need for continued exploration into the relationship between retinal structure and function in LIR, and the importance of heightened public awareness and preventive strategies to mitigate the risk of LIR.

Retinitis pigmentosa (RP) is the most common inherited blinding retinal degenerative disease characterized by the progressive loss of photoreceptors and retinal pigment epithelium (RPE) that eventually causes retinal degeneration. However, the mechanisms that initiate RP and drive retinal vulnerability remain incompletely understood, and new strategies for its prevention and therapy are urgently needed. Mitochondrial dysfunction is the initiator of a variety of neurodegeneration, whether mitochondrial dysfunction is an important pathogenic factor of RP is still unknown. Our single-cell RNA sequencing, transmission electron microscopy, and enzyme-linked immunosorbent assay revealed that both photoreceptor cells and RPE cells of RP rats have abnormal mitochondria, accompanied by decreased levels of nicotinamide adenine dinucleotide (NAD+) metabolism which rendered the lack of NAD+ vulnerable to disease-related insults. Moreover, similar experimental results were observed in an in vitro RP model established by human primary RPE cells. Furthermore, electroretinography combined with hematoxylin-eosin, immunofluorescence analysis, and fundus photograph investigations revealed that oral administration of the NAD+ precursor nicotinamide (NMN) protected RP rats against retinal degeneration. Mechanistically, single-cell RNA sequencing, siRNA targeting, and AAV virus applications demonstrated the therapeutic effect of NMN on RP through the glyceraldehyde-phosphate dehydrogenase-mitochondria pathway. Collectively, these findings indicate that mitochondrial abnormalities may be the drivers of RP and NMN has a therapeutic effect on RP.

Cataracts are the leading cause of blindness in the world. Age is a major risk factor for cataracts, and with increasing aging, the burden of cataracts will grow, but the exact details of cataractogenesis remain unclear. A recent study showed that microRNA-34a (MIR34A) is involved in the development of cataracts, but the underlying pathogenesis remains obscure. Here, our results of microRNA target prediction showed that hexokinase 1 (HK1) is one of the genes targeted by MIR34A. Based on this finding, we focused on the function of MIR34A and HK1 in the progress of cataracts, whereby the human lens epithelial cell line SRA01/04 and mouse lens were treated with MIR34A mimics and HK1 siRNA. We found that HK1 mRNA is a direct target of MIR34A, whereby the high expression of MIR34A in the cataract lens suppresses the expression of HK1. In vitro, the upregulation of MIR34A together with the downregulation of HK1 inhibits the proliferation, induces the apoptosis of SRA01/04 cells, and accelerates the opacification of mouse lenses via the HK1/caspase 3 signaling pathway. In summary, our study demonstrates that MIR34A modulates lens epithelial cell (LEC) apoptosis and cataract development through the HK1/caspase 3 signaling pathway.

Persistent idiopathic macular hole (PIMH), the occurrence of idiopathic macular holes that have failed to close after standard pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, has become a global health threat to the aging population. Because postoperative anatomic closure or restoration of visual acuity is more difficult to achieve in PIMH, surgical approaches that would yield the best outcomes remain to be elucidated. On paper, extended ILM peeling combined with silicone oil (SiO) tamponade is believed to be a feasible option for excellent macular hole closure. However, no studies on this combined treatment for PIMH is compared with simple air tamponade have been conducted. Thus, in this retrospective case series, we used spectral-domain optical coherence tomography (SD-OCT) and other technologies to investigate real-world evidence for the anatomical and functional outcomes of revisional PPV with either SiO or air tamponade for failed primary idiopathic macular hole surgery. We included the records of 76 patients with PIMH who had SD-OCT examinations and best-corrected visual acuity (BCVA). Regression analysis was performed to find factors affecting PIMH fracture closure. Seventy-six participants were allocated to a SiO group (n = 21, with an extended ILM peeling and SiO tamponade) or an air group (n = 55, with extended ILM peeling and air tamponade). Anatomical success was achieved in 18 (85.7%) and 40 (72.7%) eyes in the SiO and air groups, respectively (p = 0.37). BCVA was significantly improved in both subgroups of closed PIMH (SiO group: p = 0.041; air group: p < 0.001). Minimum linear diameter (MLD) was closely related to the closure rate (OR, 1.0; 95% CI (0.985-0.999); p = 0.03). MLD = 650 μm seemed like a cut-off point for closure rate (MLD ≤ 650 μm vs. MLD > 650 μm; 88.4% vs. 52%, p = 0.002). In conclusion, we demonstrated that extended ILM peeling combined with SiO or air tamponade is effective in PIMH treatment. Moreover, though not statistically significant herein, the anatomic closure rate was better for silicone-operated eyes than for air-operated eyes. MLD is the best predictor of PIMH closure; MLD ≤ 650 μm could achieve a significantly higher closure rate.

Uveitis is a devastating intraocular inflammatory disease. The secreted leucine‐rich repeat protein slit homologue 2 (Slit2) has been found to be an essential regulator of inflammation. This study aimed to analyse the anti‐inflammatory effects and the underlying mechanisms of Slit2 in an endotoxin‐induced uveitis (EIU) rat model. In this study, rats with EIU pretreated recombinant human Slit2 (rhSlit2) or a control vehicle by intravitreal injection. The clinical scores were graded under a slit lamp. The protein concentrations and total number of cells in the aqueous humour (AqH) were examined, and the retinal expression of various inflammatory mediators was detected. The levels of nuclear factor‐kappa B (NF‐κB), phosphorylated NF‐κB, IkappaB‐a (IκB‐a), phosphorylated IκB‐a, IKK, phosphorylated IKK, PI3Kp85, phosphorylated PI3Kp85, Akt and phosphorylated Akt were evaluated by western blotting. Treatment with rhSlit2 dramatically diminished the clinical scores of EIU, with significant decreases in inflammatory cell infiltration, protein concentrations, cellulose‐like exudates, the production of ICAM‐1, MCP‐1, TNF‐α and IL‐6 in the AqH; and adhesion of leucocytes. The PI3K/Akt/IKK/NF‐κB pathway was found to be activated in EIU. However, the pre‐treatment of rhSlit2 significantly inhibited the production of ICAM‐1, MCP‐1, TNF‐α, and IL‐6, and inhibited leucocyte adhesion by modulating the PI3K/Akt/IKK/NF‐κB pathway. In conclusion, the intravitreal injection of rhSlit2 alleviated EIU‐related inflammation in Sprague–Dawley rats by reducing the proinflammatory cytokines and leucocyte adhesion; in particular, rhSlit2 may inhibit LPS‐induced inflammation by inhibiting the activation of PI3K/Akt/IKK/NF‐κB signalling pathway. Therefore, rhSlit2 shows significant potential for effectively alleviating immune inflammatory responses in vivo.

IntroductionPhotoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations.MethodsWe established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein–protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug–gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsWe identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes.DiscussionOur findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated beta-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase (MERTK) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)-which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)-plays a vital role in phagocytosis in RPE cells. However, whether CCT5/F-actin signaling is involved in MERTK-associated RP remains largely unknown. In the present study, we specifically knocked down MERTK and CCT5 through siRNA transfection and examined the expression of CCT5 and F-actin in human primary RPE (HsRPE) cells. We found that MERTK downregulation inhibited cell proliferation, migration, and phagocytic function; significantly decreased the expression of F-actin; and disrupted the regular arrangement of F-actin. Importantly, our findings firstly indicate that CCT5 interacts with F-actin and is inhibited by MERTK siRNA in HsRPE cells. Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway. In conclusion, CCT5 protects against the effect of MERTK knockdown in HsRPE cells and demonstrates the potential for effective treatment of MERTK-associated RP.

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus and currently one of the major causes of blindness. Several previous studies have demonstrated that autophagy, which is regulated by HMGB1 (high mobility group box 1), is involved in DR development. However, the role of autophagy in DR is quite complicated in that it promotes pericyte survival in early DR, whereas excessive autophagy causes excess stress and leads to necrosis. Therefore, this study aimed to investigate the relationship between HMGB1, the macroautophagy/autophagy-lysosome pathway, and DR, as well as their underlying molecular mechanisms. In brief, the relationship between high glucose (HG) and the autophagy-lysosome pathway was examined in retinal pigment epithelial (RPE) cells. The relationship was studied by detecting classical autophagic features, and siRNAs targeting HMGB1 and pharmacological regulators were used to explore the role of the autophagy-lysosome pathway in DR development. The results demonstrated that HG inhibited autophagy and diminished the degradative capacity of autophagy due to lysosome membrane permeabilization (LMP). In addition, HMGB1 was found to be involved in LMP via the CTSB (cathepsin B)-dependent pathway, but not the CTSL (cathepsin L)-dependent pathway. Knockdown of HMGB1 expression rescued LMP, restored the degradative capacity of autophagy, decreased the expression of inflammatory factors and VEGF (vascular endothelial growth factor), and protected against apoptosis in RPE cells in the early stages of DR.

Background Earlier, we reported that the microRNA (miR)-155 expression in dendritic cells (DCs) from Behcet’s disease (BD) patients was decreased and affected cytokine production of DCs. In this study, we investigated the mechanisms whereby miR-155 regulates cytokine production by DCs. Methods The formation of autophagosomes in DCs was detected by transmission electron microscopy. Western blotting was used to detect the protein levels of LC3, Beclin-1, P62, p-mTOR, and p-Akt in DCs. TNF-α, IL-6, and IL-1β expression were investigated by ELISA. MiR-155 mimics were transfected to DCs to evaluate its effects on autophagy and cytokine production. RNA interference was used to downregulate the expression of TAB2. Results The formation of autophagosomes was found in DCs of active BD patients. The expressions of LC3-II, Beclin-1, and P62 were significantly increased in DCs of active BD patients compared to that of inactive BD patients and healthy controls. The expressions of IL-6, IL-1β, and TNF-α were significantly increased in DCs of active BD patients compared to that of healthy controls. The autophagy promoter (3-MA) and inhibitor (rapamycin) significantly decreased or increased the expression of TNF-α, IL-6, and IL-1β by DCs. The expression of LC3-II and Beclin-1 was significantly increased, but the expression of P62 proteins was decreased in DCs transfected with miR-155 mimics or after TAB2 was downregulated. The expression of TNF-α, IL-6, and IL-1β was decreased in DCs after miR-155 was upregulated or TAB2 was downregulated. The ratios of p-Akt/Akt and p-mTOR/mTOR were decreased in DCs after miR-155 was upregulated. Conclusions These results suggest that miR-155 affects the production of TNF-α, IL-6, and IL-1β by DCs through activation of the Akt/mTOR signaling pathway and by affecting the process of autophagy.

Introduction To investigate the incidence and causes of intraoperative choroidal detachment (CD) during small-gauge vitrectomy, as well as the anatomic and visual outcomes. Methods We retrospectively reviewed the medical records of 1026 consecutive patients who underwent small-gauge vitrectomy from June 2017 to December 2018 at Zhongshan Ophthalmic Centre, Guangzhou, China. Data on the presence, location, and extent of intraoperative CD and its relationship to the infusion cannula were collected. Patient demographic characteristics and postoperative anatomic and visual outcomes were also assessed. Results A total of six cases were found to have intraoperative CD, including two with serous CD, three with limited haemorrhagic CD, and one with CD caused by inadvertent perfusion of gas during air/fluid exchange. Retraction of the infusion cannula and acute ocular hypotony were found to be the main causes of intraoperative CD in five out of the six cases. The best-corrected visual acuity of all cases significantly improved after the surgery. Conclusion The incidence of intraoperative CD during small-gauge vitrectomy is low; the predominant causes are retraction of the infusion cannula and acute ocular hypotony. Immediate awareness and timely closure of the incision may contribute to a better surgical prognosis.

Background: Adipogenesis, glycosaminoglycan hyaluronan (HA) production, inflammation, and fibrosis are the main pathogenic mechanisms responsible for Graves' orbitopathy (GO). We hypothesized that disulfiram (DSF), an aldehyde dehydrogenase (ALDH) inhibitor used to treat alcoholism, would have therapeutic effects on orbital fibroblasts (OFs) in GO. This study aimed at determining the therapeutic effects and underlying mechanisms of DSF on these parameters. Methods: Primary cultures of OFs from six GO patients and six control subjects were established. The OFs were allowed to differentiate into adipocytes and treated with various concentrations of DSF. Lipid accumulation within the cells was evaluated by Oil Red O staining. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to measure the expression of key adipogenic transcription factors, ALDH1A1, ALDH2, and mitogen-activated protein kinase (MAPK) signaling proteins. Apoptosis assays and reactive oxygen species levels were evaluated by flow cytometry. HA production was measured by using an enzyme-linked immunosorbent assay (ELISA) kit. The mRNA levels of proinflammatory molecules were measured by using RT-PCR after interleukin (IL)-1β stimulation with or without DSF. The mRNA expression of markers associated with fibrosis was examined by using RT-PCR after transforming growth factor (TGF)-β1 stimulation with or without DSF. The wound-healing assay was assessed by phase-contrast microscopy. Results: Under identical adipogenesis conditions, GO OFs effectively differentiated, while normal control (NC) OFs did not. DSF dose dependently suppressed lipid accumulation during adipogenesis in GO OFs. The expression of key adipogenic transcription factors, such as perilipin-1 (PLIN1), PPARγ (PPARG), FABP4, and c/EBPα (CEBPA), was downregulated. Further, DSF inhibited the phosphorylation of ERK by inhibiting ALDH1A1. In addition, DSF attenuated HA production and suppressed inflammatory molecule expression induced by IL-1β in GO OFs and NC OFs. The antifibrotic effects of DSF on TGF-β1 were also observed in GO OFs. Conclusions: In the current study, we provide evidence of the inhibitory effect of DSF on GO OFs adipogenesis, HA production, inflammation, and fibrosis in vitro. The results of this study are noteworthy and indicate the potential use of DSF as a therapeutic agent for the treatment of GO.

糖尿病视网膜病变(diabetic retinopathy,DR)是由糖尿病所导致的最典型的微血管并发症之一.以往DR发病机制和治疗的研究主要集中在微血管;近年来,许多学者认为DR不仅仅是一种微血管病变,而且还伴有视网膜神经退行性变.近期研究表明,自噬与高迁移率族蛋白B1(high mobility group box protein 1,HMGB1)通过多条通路参与到糖尿病视网膜微血管病变和神经退行性变中,通过调控自噬或HMGB1可能为DR治疗提供一种新的思路.本文就自噬与HMGB1在糖尿病视网膜微血管病变和神经退行性变发病中的研究进展进行综述.

Purpose: To investigate the role of G-protein-coupled bile acid receptor-1, Gpbar1 (TGR5) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.Methods: The mRNA level of TGR5, iNOS, Arg1, CD16, and CD206 in macrophages was assayed by real-time PCR. ELISA was used to detect the production of cytokines in cell culture supernatants. The frequencies of CD4+IFN-γ+ and CD4+ IL-17+ T cells were tested by flow cytometry.Results: A decreased expression of TGR5 in M1 macrophages was observed in active VKH patients as compared with normal controls. TGR5 stimulation of M1 macrophages with INT-777 caused a shift of the inflammatory M1 toward the anti-inflammatory M2 macrophage subtype. TGR5 activation of macrophages co-cultured with CD4+ T cells inhibited Th1 and Th17 polarization, as well as the release of IFN-γ and IL-17 in the culture supernatant.Conclusion: Our results show that a decreased TGR5 expression might contribute to the pathogenesis of VKH disease.