Increased serum urea and creatinine levels correlate with decreased retinal nerve fibre layer thickness in diabetic retinopathy

Srivastav, Khushboo; Saxena, Sandeep; Mahdi, Abbas Ali; Kružliak, Peter; Khanna, Vinay K.

doi:10.3109/1354750x.2015.1094142

Cited by 37 publications

(41 citation statements)

References 29 publications

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“…[28]The regulation of blood flow was considered in response to neuroactivity. However, recent research has pointed out that retinal neurodegeneration might precede microvascular dysfunction in DR. [29][30][31][32] Studies also have found out that RNFL thinning correlated positively with severity of DR. [33] In the present research, we also documented significant difference in average RNFL thickness in-between group comparison. RNFL thickness reduced as the severity of DR increased.…”

Section: Discussionsupporting

confidence: 75%

Macular and peripapillary vessel density measurement in the evaluation of Non-proliferative Diabetic Retinopathy

Yang

Cao

et al. 2019

Preprint

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Purpose: To compare vessel density in macular and peripapillary area between control subjects and patients with non-proliferative diabetic retinopathy (NPDR) using optical coherence tomography angiography (OCTA) and to evaluate the association between RNFL thickness and different stage of diabetic retinopathy. Methods: A total of 170 eyes (normal control, 43; mild NPDR, 43; moderate NPDR, 42; severe NPDR, 42) underwent OCTA imaging. Optical coherence tomography angiographic parameters were vessel densities of superficial capillary plexus (SCP), deep capillary plexus (DCP) in macular area and peripapillary area. Results: Vessel density of SCP and DCP in macular area, peripapillary area as well as RNFL thickness were 53.13%±3.03%, 52.07%±2.28%, 53.78%±3.66% and 128.86μm±11.32μm, respectively, in control subjects; 50.24%±3.81%, 47.40%±45.02%, 46.50%±6.03% and 124μm±13.97μm, respectively, in mild NPDR; 46.80%±5.23%; 44.39%±3.99%; 44.64%±4.23%; 121.02μm±20.86μm, respectively, in moderate NPDR; 42.82%±5.46%, 42.34%±5.14%, 43.16%±4.47%, 118.60μm±21.91μm in severe NPDR. The reduction of vessel density of SCP and DCP in macular area, peripapillary area as well as RNFL thickness were correlated with increasing severity of DR. Vessel density of SCP and DCP in macular area, peripapillary area and foveal density 300 (FD 300) in normal control were significantly higher than that of mild, moderate and severe NPDR groups. (all P<0.001). Vessel density of DCP shows better ability to identify the severity of DR (0.913; 95% CI=0.867-0.958; cut off value:0.75) than FD 300, vessel density of SCP in macular area and peripapillary area. Conclusion: Macular and peripapillary vessel density as well as RNFL thickness decreased as DR progresses. Vessel density in DCP could be an objective and sensitive indicator for monitoring progression of DR. OCTA might be clinically useful to evaluate microvascular and microstructural alterations in macula and optive nerve head (ONH), thus providing a new method to study the course of DR.

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Section: Discussionsupporting

confidence: 75%

Macular and peripapillary vessel density measurement in the evaluation of Non-proliferative Diabetic Retinopathy

Yang

Cao

et al. 2019

Preprint

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“…These Homocysteine is a sulfur-containing amino acid, and its high circulating levels are considered as a risk factor for many diseases including heart disease and diabetic complications [7,9]. Moderate increase in circulating homocysteine is considered to play a role in retinal abnormalities including endothelial cell dysfunction, ischemia, thinning of nerve fiber layers, neovascularization and blood-retinal barrier breakdown, the abnormalities intimately associated with diabetic retinopathy [40,41]. Our results show that the donors with established diabetic retinopathy have higher homocysteine levels in their retinal microvasculature, the site of retinal histopathology characteristic of diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Faulty homocysteine recycling in diabetic retinopathy

2020

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Background: Although hyperglycemia is the main instigator in the development of diabetic retinopathy, elevated circulating levels of a non-protein amino acid, homocysteine, are also associated with an increased risk of retinopathy. Homocysteine is recycled back to methionine by methylenetetrahydrofolate reductase (MTHFR) and/or transsulfurated by cystathionine β-synthase (CBS) to form cysteine. CBS and other transsulfuration enzyme cystathionine-γ-lyase (CSE), through desulfuration, generates H 2 S. Methionine cycle also regulates DNA methylation, an epigenetic modification associated with the gene suppression. The aim of this study was to investigate homocysteine and its metabolism in diabetic retinopathy. Methods: Homocysteine and H 2 S levels were analyzed in the retina, and CBS, CSE and MTHFR in the retinal microvasculature from human donors with established diabetic retinopathy. Mitochondrial damage was evaluated in retinal microvessels by quantifying enzymes responsible for maintaining mitochondrial dynamics (fission-fusionmitophagy). DNA methylation status of CBS and MTHFR promoters was examined using methylated DNA immunoprecipitation technique. The direct effect of homocysteine on mitochondrial damage was confirmed in human retinal endothelial cells (HRECs) incubated with 100 μM L-homocysteine. Results: Compared to age-matched nondiabetic control human donors, retina from donors with established diabetic retinopathy had~3-fold higher homocysteine levels and~50% lower H 2 S levels. The enzymes important for both transsulfuration and remethylation of homocysteine including CBS, CSE and MTHFR, were 40-60% lower in the retinal microvasculature from diabetic retinopathy donors. While the mitochondrial fission protein, dynamin related protein 1, and mitophagy markers optineurin and microtubule-associated protein 1A/1B-light chain 3 (LC3), were upregulated, the fusion protein mitofusin 2 was downregulated. In the same retinal microvessel preparations from donors with diabetic retinopathy, DNA at the promoters of CBS and MTHFR were hypermethylated. Incubation of HRECs with homocysteine increased reactive oxygen species and decreased transcripts of mtDNA-encoded CYTB. Conclusions: Compromised transsulfuration and remethylation processes play an important role in the poor removal of retinal homocysteine in diabetic patients. Thus, regulation of their homocysteine levels should ameliorate retinal mitochondrial damage, and by regulating DNA methylation status of the enzymes responsible for homocysteine transsulfuration and remethylation, should prevent excess accumulation of homocysteine.

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“…This finding suggests that there may be an association between renal function and retinal neuropathy. Srivastav et al 83 found an association between increased serum urea and creatinine levels and decreased RNFL thickness in patients with diabetes, while Shim et al 84 recently demonstrated that low eGFR levels are independently associated with POAG. However, there is a paucity of data regarding this potential association in the absence of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

et al. 2017

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IMPORTANCE Measurement of ganglion cell complex (GCC) thickness may be more sensitive than current methods for glaucoma diagnosis and research. However, little is known about the factors influencing GCC thickness in the general population.OBJECTIVES To investigate the heritability of and factors associated with GCC thickness in a healthy aging population. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional twin study was conducted from August 27, 2014, to March 31, 2016, among 1657 participants of white British ancestry from the TwinsUK study cohort without ocular pathologic conditions. Heritability analyses were conducted in 1432 twins (426 monozygous and 290 dizygous pairs). Association analyses were performed using univariable and multivariable stepwise linear regression models, taking family structure into account. Heritability analyses were conducted using maximum likelihood structural equation twin modeling. MAIN OUTCOMES AND MEASURESParameters measured included GCC thickness, autorefraction, intraocular pressure, blood pressure, body mass index, and cholesterol, creatinine, glucose, insulin, triglycerides, and urea levels. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. RESULTS Among the 1657 participants (mean [SD] age, 56.0 [15.3] years; 89.5% women and 10.5% men), the mean [SD] inner GCC thickness was 96.0 [7.6] μm (95% CI, 95.1-96.2). In multivariable modeling, the mean inner GCC thickness was associated with advancing age (β, -0.14; P < .001), increased body mass index (β, -0.15; P = .001), spherical equivalent (β, 0.70; P < .001), and higher estimated glomerular filtration rate (β, 0.03; P = .02). A 1-U increase in age or body mass index was associated with a 0.14-μm and 0.15-μm decrease in GCC thickness, respectively (P < .001), while a 1-U increase in spherical equivalent or estimated glomerular filtration rate was associated with a 0.70-μm (P < .001) and 0.03-μm (P = .02) increase in GCC thickness, respectively. Ganglion cell complex thickness was not associated with sex, intraocular pressure, or diabetes. Age-adjusted GCC thickness was highly heritable, with additive genetic effects explaining 81% (95% CI, 78%-84%) of phenotypic variance and individual environmental factors explaining the remaining 19% (95% CI, 16%-22%).CONCLUSIONS AND RELEVANCE Ganglion cell complex thickness appears to be highly heritable and further genetic analysis may help identify new biological pathways for glaucoma. The results suggest it may be important to account for age, body mass index, refractive error, and sex when using GCC thickness as a diagnostic tool. Replication of their results is required, as is further research to explain the association between renal function and GCC thickness.

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Increased serum urea and creatinine levels correlate with decreased retinal nerve fibre layer thickness in diabetic retinopathy

Cited by 37 publications

References 29 publications

Macular and peripapillary vessel density measurement in the evaluation of Non-proliferative Diabetic Retinopathy

Macular and peripapillary vessel density measurement in the evaluation of Non-proliferative Diabetic Retinopathy

Faulty homocysteine recycling in diabetic retinopathy

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

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