Characterization of Vitreous and Aqueous Proteome in Humans With Proliferative Diabetic Retinopathy and Its Clinical Correlation

Balaiya, Sankarathi; Zhou, Zimei; Chalam, Kakarla V

doi:10.1177/1178641816686078

Cited by 39 publications

(50 citation statements)

References 33 publications

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“…We hypothesize that diabetic aqueous accumulates inflammatory proteins due to blood-aqueous barrier breakdown and poses a similar risk for inflammation mediated impairment in corneal endothelial cell health and poor graft function in this disease impaired anterior segment environment. Diabetes has already been shown to increase the total protein and alter the protein profile of aqueous humor 3 , 4 . While there are supportive clinical findings both in our study and the Price study, this hypothesis remains speculative and needs further investigation.…”

Section: Discussionsupporting

confidence: 70%

DMEK outcomes using nondiabetic grafts for recipients with diabetes mellitus

Janson

Terveen

Benage

et al. 2019

American Journal of Ophthalmology Case Reports

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Purpose To compare Descemet membrane endothelial keratoplasty (DMEK) outcomes using nondiabetic grafts in diabetic and nondiabetic recipients. Methods All eyes that underwent DMEK between February 2013 and October 2016 (follow-up ≥3 months, without prior keratoplasty) were included. Recipients were divided into diabetic (insulin dependent [IDDM] or noninsulin dependent [NIDDM]) and nondiabetic groups. Main outcome measures included postoperative visual acuity, rebubble procedure rates, and graft failure rates. Results Of 334 eyes (243 subjects) included for analysis, 63 eyes (18.8%) were from diabetic recipients. At each timepoint, best-corrected visual acuity trended lower for IDDM recipients compared to NIDDM and nondiabetic recipients. There were no statistically significant differences in rebubble rates of diabetic compared to nondiabetic recipients (20.6% vs. 12.9%, p = 0.17), or IDDM compared to nondiabetic recipients (27.3% vs. 12.9%, p = 0.08; hazard ratio 2.26). Overall, 13 grafts (3.9%) failed (mean follow-up, 565 days; range, 90–1293 days). Graft failures did not differ between diabetic and nondiabetic recipients (4.0% vs. 4.9%, p = 0.15) regardless of subgroup (p = 0.36). Conclusions DMEK provides excellent outcomes for patients with and without diabetes. DMEK outcomes were excellent with improvements in visual acuity and low rates of graft failure. Our findings were unable to determine differences between rebubble procedure rates but do emphasize the need for further research using stratified groups based on diabetes severity.

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Section: Discussionsupporting

confidence: 70%

DMEK outcomes using nondiabetic grafts for recipients with diabetes mellitus

Janson

Terveen

Benage

et al. 2019

American Journal of Ophthalmology Case Reports

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“…The complement system, besides having a major role as an immune defense mechanism, is involved in several tissue-remodeling processes, such as liver regeneration and synaptic pruning during development, and also in retinal angiogenesis and neurodegenerative diseases (8)(9)(10)(11). The role of the complement system in angiogenesis is of prime importance, since there are several eye diseases associated with abnormal ocular angiogenesis and neurodegeneration, such as retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and proliferative diabetic retinopathy (PDR) (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy

et al. 2020

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The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both the classical and alternative pathways in vitreous humor and serum samples from proliferative DR (PDR) patients and controls. Further, the expressions of complements and several other key pro-and anti-angiogenic genes in the serum and vitreous humor were analyzed in the blood samples of PDR and non-PDR (NPDR) patients along with controls without diabetes. We also assessed the pro-inflammatory cytokines and matrix metalloproteinases in the vitreous humor samples. There was a significant increase in C3 and its activated fragment C3bα' (110 kDa) along with a corresponding upregulation of CFH in the vitreous of PDR patients, which confirmed the increased activation of the alternative complement pathway in PDR. Likewise, a significant upregulation of angiogenic genes and downregulation of anti-angiogenic genes was seen in PDR and NPDR cases. Increased MMP9 activity and upregulation of inflammatory markers IL8 and sPECAM with a downregulation of anti-inflammatory marker IL-10 in PDR vitreous indicated the possible involvement of microglia in DR pathogenesis. Further, a significantly high C3 deposition in the capillary wall along with thickening of basement membranes and co-localization of CFH expression with CD11b +ve activated microglial cells in diabetic retina suggested microglia as a source of CFH in diabetic retina. The increased CFH levels could be a feedback mechanism for arresting excessive complement activation in DR eyes. A gradual increase of CFH and CD11b expression in retina with early to late changes in epiretinal membranes of DR patients indicated a major role for the alternative complement pathway in disease progression.

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“…MS-based proteomics is of great value to study different ocular diseases such as cataracts [ 12 ], age-related macular degeneration (AMD) [ 13 , 14 ] and DR [ 15 , 16 ]. Despite the great efforts that have been devoted to DR vitreous protein identification [ 17 , 18 ], we are still far from a comprehensive understanding of the complex molecular pathomechanisms. Quantitative proteomics is an analytical chemistry technique for determining the amount of proteins, which can contribute to better insight into the underlying pathogenesis [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomics analysis of vitreous body from type 2 diabetic patients with proliferative diabetic retinopathy

2018

BMC Ophthalmol

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BackgroundTo compare the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH).MethodsIn this study, we performed mass spectrometry-based label-free quantitative proteomics analysis of vitreous samples from type 2 diabetic patients with PDR (n = 9) and IMH subjects (n = 9) and identified the abundance of 610 proteins.ResultsOut of 610 proteins, 64 proteins (Group A) were unique to PDR patients, while 212 proteins (Group B) could be identified in IMH vitreous only. Among the other 334 proteins that could be detected in both PDR and IMH eyes, 62 proteins differed significantly (p < 0.05, fold change > 2), which included 52 proteins (Group C) and 10 proteins (Group D) over- and under-expressed in PDR vitreous compared with the control. All proteins in these four groups were counted as significant proteins in our study.ConclusionsWe identified and quantified 610 proteins in total, which included 338 significant proteins in our study. Protein distribution analysis demonstrated a clear separation of protein expression in PDR and IMH. The protein function analysis illustrated that immunity and transport related proteins might be associated with PDR.

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Characterization of Vitreous and Aqueous Proteome in Humans With Proliferative Diabetic Retinopathy and Its Clinical Correlation

Cited by 39 publications

References 33 publications

DMEK outcomes using nondiabetic grafts for recipients with diabetes mellitus

DMEK outcomes using nondiabetic grafts for recipients with diabetes mellitus

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy

Quantitative proteomics analysis of vitreous body from type 2 diabetic patients with proliferative diabetic retinopathy

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