Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.
To investigate retinal neurovascular structural changes in patients with essential hypertension. METHODS. This observational cross-sectional study consisted of 199 right eyes from 169 nondiabetic essential hypertensive patients, divided into groups as follows: group A, 113 patients with hypertensive retinopathy (HTNR); group B, 56 patients without HTNR; and a control group of 30 healthy subjects. Peripapillary retinal nerve fiber layer (RNFL), radial peripapillary segmented (RPC), ganglion cell-inner plexiform layer (GC-IPL), and superficial (SVP) and deep (DVP) vascular plexus density at the macula (6 × 6 mm 2) were measured by optical coherence tomography angiography (OCTA). RESULTS. DVP density was significantly reduced in groups A and B compared to the control group (group A DVP, P = 0.001; group B DVP P = 0.002). GC-IPL, RNFL thickness, and RPC and SVP density in group A were significantly decreased compared to the control group or group B (all P < 0.05). In hypertensive patients, GC-IPL and RNFL thickness were negatively correlated with severity of HTNR (GC-IPL, r =-0.331, P < 0.001; RNFL, r =-0.583, P < 0.001) and level of home blood pressure monitoring (HBPM)
ONH perfusion and peripapillary RNFL thickness were significantly decreased in preclinical DR patients compared to normal controls. Microvascular alterations in ONH may occur earlier than peripapillary RNFL defect in the course of DR.
Diabetic retinopathy is the leading cause of blindness in working age individuals in developed countries. However, the role of inflammation in the pathogenesis of DR is not completely understood. This is an observational clinical research enrolling 80 type II diabetic patients who had undergone cataract surgeries either with DR or without DR. All cases were further categorized by the proliferative stages of retinal neovascularization and by the lengths of diabetic history. The levels of inflammatory cytokines including IL-1β, IL-6, IL-8, IL-17, and TNF-α in aqueous humour were tested. Results in this study indicated that these cytokine levels were increased in DR patients and might have a synergistic effect on the pathogenesis of this disease. They were also elevated along with the progression of neovascularization, reflecting the severity of DR. The results also suggested that for diabetic patients, the higher these levels are, the sooner retinal complications might appear. In conclusion, the levels of inflammatory cytokines IL-1β, IL-6, IL-8, IL-17A, and TNF-α in aqueous humour may be associated with the pathogenesis, severity, and prognosis of DR.
The complex drug delivery barrier in the eye reduces the bioavailability of many drugs, resulting in poor therapeutic effects. It is necessary to investigate new drugs through appropriate delivery routes and vehicles. Nanotechnology has utilized various nano-carriers to develop potential ocular drug delivery techniques that interact with the ocular mucosa, prolong the retention time of drugs in the eye, and increase permeability. Additionally, nano-carriers such as liposomes, nanoparticles, nano-suspensions, nano-micelles, and nano-emulsions have grown in popularity as an effective theranostic application to combat different microbial superbugs. In this review, we summarize the nano-carrier based drug delivery system developments over the last decade, particularly review the biology, methodology, approaches, and clinical applications of nano-carrier based drug delivery system in the field of ocular therapeutics. Furthermore, this review addresses upcoming challenges, and provides an outlook on potential future trends of nano-carrier-based drug delivery approaches in ophthalmology, and hopes to eventually provide successful applications for treating ocular diseases.
Background and objectivesThe association of diabetic retinopathy (DR) and diabetic macular oedema (DME) with renal function in southern Chinese patients with diabetes is poorly understood. So we aimed to study the correlation between stage of DR and DME with stage of estimated glomerular filtration rate (eGFR) and stage of urine albumin-to-creatinine ratio (UACR), and to explore the systemic risk factors for DR and DME.Design and settingThis single-centre retrospective observational study was conducted from December 2017 to November 2018.Participants413 southern Chinese patients with type 2 diabetes mellitus.Outcome measuresThe correlations between stage of DR and DME with stage of eGFR/UACR were assessed by Spearman’s or χ² analyses and represented with histograms. Risk factors associated with the occurrence of DR and DME were performed by logistic regression and represented with nomograms.ResultsStage of DR had a positive correlation with stage of eGFR (r=0.264, p<0.001) and stage of UACR (r=0.542, p<0.001). With the stage of eGFR/UACR being more severe, the prevalence of DME became higher as well (both p<0.001). The risk factors for DR were DM duration (OR 1.072; 95% CI 1.032 to 1.114; p<0.001), stage of UACR (OR 2.001; 95% CI 1.567 to 2.555; p<0.001) and low-density lipoprotein (LDL) (OR 1.301; 95% CI 1.139 to 1.485; p<0.001), while risk factors for DME were stage of UACR (OR 2.308; 95% CI 1.815 to 2.934; p<0.001) and LDL (OR 1.460; 95% CI 1.123 to 1.875; p=0.008).ConclusionsAmong southern Chinese patients, stage of DR and DME were positively correlated with renal function, while stage of UACR performed a better relevance than stage of eGFR.
Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.
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