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→Mild or moderate NPDR: revised citations to mention of role for fenofibrate. |
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==Pathogenesis==
[[File:Blausen 0312 DiabeticRetinopathy.png|thumb|Illustration depicting diabetic retinopathy]]
Diabetic retinopathy is the result of damage to the small blood vessels and neurons of the retina. The earliest changes leading to diabetic retinopathy include narrowing of the retinal arteries associated with [[Ischemia|reduced retinal blood flow]]; dysfunction of the neurons of the inner retina, followed in later stages by changes in the function of the outer retina, associated with subtle changes in visual function; dysfunction of the [[blood-retinal barrier]], which protects the retina from many substances in the blood (including toxins and [[immune cells]]), leading to the leaking of blood constituents into the retinal [[neuropile]].<ref name="XuCurtisStitt">{{cite journal| vauthors = Xu H, Curtis T, Stitt A |title=Pathophysiology and Pathogenesis of Diabetic Retinopathy [internet] |journal= Diapedia|date=13 August 2013 |volume=7104343513 |issue=14 |doi=10.14496/dia.7104343513.14|doi-broken-date=2024-
An experimental study suggests that pericyte death is caused by blood glucose persistently activating [[protein kinase C]] and [[mitogen-activated protein kinase]] (MAPK), which, through a series of intermediates, inhibits signaling through [[platelet-derived growth factor receptor]]s—signaling that supports cellular survival, proliferation, and growth. The resulting withdrawal of this signaling leads to the programmed cell death ([[apoptosis]]) of the cells in this experimental model.<ref>{{cite journal | vauthors = Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, Clermont A, Leitges M, Marette A, Aiello LP, Kern TS, King GL | display-authors = 6 | title = Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy | journal = Nature Medicine | volume = 15 | issue = 11 | pages = 1298–1306 | date = November 2009 | pmid = 19881493 | pmc = 3290906 | doi = 10.1038/nm.2052 }}</ref>
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===Mild or moderate NPDR===
For those with mild to moderate non-proliferative diabetic retinopathy, the American Academy of Ophthalmology recommends only more frequent retinal exams—every six to twelve months—as these people are at an increased risk of developing proliferative retinopathy or macular edema.{{sfn|Flaxel|Adelman|Bailey|Fawzi|2020|loc="Mild to moderate NPDR without macular edema"}} Injection of [[anti-VEGF]] drugs or steroids can reduce diabetic retinopathy progression in around half of eyes treated; however, whether this results in improved vision long term is not yet known.{{sfn|Brownlee|Aiello|Sun|Cooper|2020|loc="Treatment of nonproliferative diabetic retinopathy”}} The lipid-lowering drug [[fenofibrate]] also reduces progression of disease in people with mild to moderate disease.<ref>{{Cite journal |
===Diabetic macular edema===
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