Retinal neurodegeneration in metabolic syndrome:a spectral optical coherence tomography study

AIM:To evaluate the effects of metabolic syndrome(Met S)on retinal neurodegeneration by optical coherence tomography(OCT).METHODS:Patients diagnosed as Met S were compared with the age and sex-matched healthy control group(CG).Waist circumference measurements,fasting serological biochemical tests,and systemic blood pressures of all participants were evaluated.The Met S group was divided into 3 subgroups according to the number of Met S components:hypertension,diabetes mellitus,dyslipidemia(low-,high-density lipoprotein,hypertriglyceridemia),and visceral obesity findings;3-component Met S3,4-component Met S4,and all-component Met S5.All patients underwent complete eye examination and spectral OCT retinal imaging.RESULTS:Totally 58 eyes of 58 patients were included in the Met S group and 63 eyes of 63 age and sex-matched healthy subjects were included in CG.Met S group was composed of 22 subjects in Met S3,21 subjects in Met S4,and 15 subjects in the Met S5 subgroup.Mean foveal thickness(Met S,218.7±23.1μm vs CG,228.8±21.9μm,P=0.015),mean inferior(Met S,283.4±17.0μm vs CG,288.7±38.4μm,P=0.002),superior(Met S,287.0±18.5μm vs CG 297.3±17.1μm,P=0.001),nasal(Met S 287.3±16.7μm vs CG 297.9±13.9μm,P=0.000)and temporal(274.5±17.6μm vs CG 285.6±13.6μm,P=0.000)thickness in the 3 mm Early Treatment of Diabetic Retinopathy Study(ETDRS)circle was significantly lower in the Met S group.There was no statistically significant difference in the mean inferior,superior,nasal,and temporal thickness of 6 mm ETDRS circle,total macular volume,peripapillary and macular retinal nerve fiber layer,macular ganglion cell layer with inner plexiform layer,and ganglion cell complex.No statistically significant difference was found in these values between the Met S3,Met S4,and the Met S5 groups.CONCLUSION:A significant reduction in central macular region thickness in Met S is detected and macular thickness is more susceptible to Met S induced neurodegeneration than peripapillary retinal nerve fiber layer.

Exploration of the glutamate-mediated retinal excitotoxic damage: a rat model of retinal neurodegeneration

AIM： To explore the more suitable concentration of glutamate or N-methyl-D-aspartic acid（NMDA） for intravitreal injection to establish a rat model of retinal neurodegeneration. METHODS： We injected different doses of glutamate（20 or 50 nmol） or NMDA（40 nmol） into the vitreous chambers of rats, then measured the concentration of glutamate and retinal thickness, quantified apoptotic cells and determined the degree of tau hyperphosphorylation at different time points. T-test was used for comparison of two groups. One-way ANOVA and Turkey＇s multiple comparisons test were used for comparisons of different groups, and P values below 0.05 were considered statistically significant.RESULTS： The glutamate level in the rats treated with 50 nmol of glutamate was twice that of the control group and persisted two weeks. Seven days after intravitreal injection of 50 nmol of glutamate, three parameters [inner retinal thickness（IRT）, retinal thickness（RT） and ganglion cell layer（GCL） cell number] were reduced significantly. Furthermore, numerous TUNEL-positive cells were observed in the GCL one day after intravitreal injection of 50 nmol of glutamate, the expression of the apoptosisrelated factor cleaved casepase-3 was markedly increased compared with the expression levels in the other treatment groups, and the expression levels of tau s396 and tau s404 were significantly increased compared with those in the control group.CONCLUSION： This study demonstrates that the intravitreal injection of 50 nmol of glutamate can establish the more effective retinal neurodegeneration animal model relative to other treatment groups.

Neurodegeneration:An early event of diabetic retinopathy

Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.

Starburst amacrine cells,involved in visual motion perception,lose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients

Background The main clinical symptoms characteristic of Parkinson’s disease(PD)are bradykinesia,tremor,and other motor deficits.However,non-motor symptoms,such as visual disturbances,can be identified at early stages of the disease.One of these symptoms is the impairment of visual motion perception.Hence,we sought to determine if the starburst amacrine cells,which are the main cellular type involved in motion direction selectivity,are degenerated in PD and if the dopaminergic system is related to this degeneration.Methods Human eyes from control(n=10)and PD(n=9)donors were available for this study.Using immunohistochemistry and confocal microscopy,we quantified starburst amacrine cell density(choline acetyltransferase[ChAT]-positive cells)and the relationship between these cells and dopaminergic amacrine cells(tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses)in cross-sections and wholemount retinas.Results First,we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins.Both populations are affected in PD and their density is reduced compared to controls.Also,we report,for the first time,synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina.We found that,in PD retinas,there is a reduction of the dopaminergic synaptic contacts into ChAT cells.Conclusions Taken together,this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells.Since motion perception circuitries are affected in PD,their assessment using visual tests could provide new insights into the diagnosis of PD.