title: Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro.
abstract: Diabetes of even short duration accelerates the death of capillary cells and neurons in the inner retina by a process consistent with apoptosis. We examined whether the process is accompanied by changes in the expression of endogenous regulators of apoptosis. In postmortem retinas of 18 diabetic donors (age 67 +/- 6 years, diabetes duration 9 +/- 4 years) the levels of pro-apoptotic Bax were slightly, but significantly, increased when compared with levels in 20 age-matched nondiabetic donors (P = 0.04). In both groups, Bax localized to vascular and neural cells of the inner retina. Neither pro-apoptotic Bcl-X(S), nor pro-survival Bcl-X(L) appeared affected by diabetes. The levels of these molecules could not be accurately quantitated in lysates of retinal vessels because of variable degrees of glial contamination. However, studies in situ showed in several pericytes, the outer cells of retinal capillaries, intense Bax staining often in conjunction with DNA fragmentation. Bovine retinal pericytes exposed in vitro to high glucose levels for 5 weeks showed elevated levels of Bax (P = 0.03) and increased frequency of annexin V binding, indicative of early apoptosis. Hence, human diabetes selectively alters the expression of Bax in the retina and retinal vascular pericytes at the same time as it causes increased rates of apoptosis. The identical program induced by high glucose in vitro implicates hyperglycemia as a causative factor in vivo, and provides a model for establishing the role of Bax in the accelerated death of retinal cells induced by diabetes.
authors.affiliation: Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: F
authors.initials: F
authors.lastname: Podestà
authors.forename: G
authors.initials: G
authors.lastname: Romeo
authors.forename: W H
authors.initials: WH
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Krajewski
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: C
authors.initials: C
authors.lastname: Gerhardinger
authors.forename: M
authors.initials: M
authors.lastname: Lorenzi
mesh_terms: D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008969:Molecular Sequence Data; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D017304:Annexin A5; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D005947:Glucose