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Jeya Maheshwari Jayapal, Roopesh R Pai, Naveen Luke Demonte, Vignesh P, Bhanu Pratap Phangtey, Kim Ramasamy, Dharmalingam Kuppamuthu; Analysis of fluid phase complement system activation in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5360.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is a global health problem that affects nearly 21% of diabetic individuals of which 9% develop vision-threatening condition. Inflammation plays a major role in the onset and progression of DR and this process is actively regulated by the complement system. Studies using human donor eyes and animal model have shown that complement system is activated in early stages of diabetic retinopathy. The objective of this study is to examine the activation of the complement system in different stages of DR and its relevance to disease progression.
Blood samples were collected from six groups representing DR progression - non-diabetic, pre-diabetic, type II diabetic (DM without DR), NPDR-mild, NPDR-moderate, PDR. Through 1D and 2D based mass spectrometry approaches, a discovery phase study was carried out with albumin and IgG-depleted serum from DM and PDR patients to identify changes in the complement proteins and proteoforms. Western blot was used quantify C3 and its processed forms in serum from all six groups.
Complement proteins, namely C3, C4, C5, C7, C8 were detected at higher levels in the serum of PDR patients when compared to that of DM. Factor B (CFB), an important component of alternative pathway was upregulated while the negative regulator of this pathway, factor I was downregulated. Many of these complement proteins exist as multiple proteoforms and interestingly, we found differential regulation of proteoforms also. Further, differential processing of the central complement protein C3 was also observed and we quantified C3dg levels to determine the extent of complement activation. The mean C3dg value was able to segregate patients in each sample category to high and low C3dg groups, with higher C3dg level representing greater activation of complement. The relevance of C3dg to DR progression will be discussed.
The complement system is activated during DR through both classical and lectin pathways. The extent of complement activation might be useful in predicting the progression of DR.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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