Editing Diabetic retinopathy (section)

==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=1 November 2024 |url=http://www.diapedia.org/acute-and-chronic-complications-of-diabetes/7104343513/pathophysiology-of-diabetic-retinopathy|access-date=26 August 2016}}</ref> Later, the basement membrane of the retinal blood vessels thickens, [[capillaries]] degenerate and lose cells, particularly [[pericytes]] and vascular [[smooth muscle cells]]. This leads to loss of blood flow and progressive [[ischemia]], and microscopic [[aneurysm]]s which appear as balloon-like structures jutting out from the capillary walls, which recruit inflammatory cells; and advanced dysfunction and degeneration of the [[neurons]] and [[glia]]l cells of the retina.<ref name="XuCurtisStitt"/><ref>{{Cite journal|title=Understanding diabetic retinopathy | vauthors = Pardianto G |journal=Mimbar Ilmiah Oftalmologi Indonesia |year=2005 |volume=2 |pages=65–6}}</ref> The condition typically develops about 10–15 years after receiving the diagnosis of diabetes mellitus.

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 | 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>

In addition, excessive [[sorbitol]] in diabetics is deposited on retina tissue and it is also proposed to play a role in diabetic retinopathy.<ref name="pmid24563789">{{cite journal | vauthors = Tarr JM, Kaul K, Chopra M, Kohner EM, Chibber R | title = Pathophysiology of diabetic retinopathy | journal = ISRN Ophthalmology | volume = 2013 | pages = 343560 | date = 2013 | pmid = 24563789 | pmc = 3914226 | doi = 10.1155/2013/343560 | doi-access = free }}</ref>

Recent studies have found a strong correlation between retinal inflammation and diabetic retinopathy progression.<ref>{{cite journal | vauthors = Shivashankar G, Lim JC, Acosta ML | title = Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model | journal = Journal of Ophthalmology | volume = 2023 | pages = 7893104 | date = 2023-02-28 | pmid = 36895267 | pmc = 9991478 | doi = 10.1155/2023/7893104 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shivashankar G, Lim JC, Acosta ML | title = Proinflammatory cytokines trigger biochemical and neurochemical changes in mouse retinal explants exposed to hyperglycemic conditions | journal = Molecular Vision | volume = 26 | pages = 277–290 | date = 2020 | pmid = 32300272 | pmc = 7155896 }}</ref>

A genetic study showed that diabetic retinopathy shares a similar genetic predisposition with levels of [[glucose]], [[low-density lipoprotein cholesterol]], and [[systolic blood pressure]],<ref name=":4" /> indicating that glycemic control and cardiometabolic factors may be important in the development of diabetic retinopathy.

[[Lipid peroxidation]] plays a notable role in the progression of diabetic retinopathy. [[Free radical]]s such as hydroxyl and hydroperoxyl species with oxygen as functional group oxidize lipids and phospholipids, and at cellular level bring about membrane lipid peroxidation and in this way can trigger diabetic retinopathy.<ref>{{cite journal | vauthors = Njie-Mbye YF, Kulkarni-Chitnis M, Opere CA, Barrett A, Ohia SE | title = Lipid peroxidation: pathophysiological and pharmacological implications in the eye | journal = Frontiers in Physiology | volume = 4 | pages = 366 | date = December 2013 | pmid = 24379787 | pmc = 3863722 | doi = 10.3389/fphys.2013.00366 | doi-access = free }}</ref>