Diabetes has an additive effect on neural apoptosis in rat retina with chronically elevated intraocular pressure.
OBJECTIVE
Diabetes mellitus (DM) is a risk factor for open-angle glaucoma, although the mechanistic interrelationship of the two is debatable. The purpose of this study is to test whether DM augments neural apoptosis in rat retina with chronically elevated intraocular pressure (IOP).


METHODS
Sprague-Dawley rats were made diabetic by intraperitoneal injection of streptozotocin (STZ). At one month after STZ injection, three episcleral veins in one eye were cauterized to elevate IOP. Rats without STZ injection were treated likewise as diabetic controls. At 2 weeks, 1 month, and 2 months after cauterization, the retina was dissected, flat-mounted, and subjected to terminal dUTP nick end labeling (TUNEL) staining. TUNEL positive cells per unit area of the whole retina were measured.


RESULTS
DM did not affect base line IOP or augment IOP elevation due to episcleral vein cauterization. TUNEL positive cells, which primarily consisted of the neurons and glial cells in the inner retina including retinal ganglion cell (RGC), were counted consistently eight times more in the diabetic retina without IOP elevation than diabetic controls (n = 9, p < 0.001). The cauterization significantly elevated IOP up to 28.9 mmHg (p < 0.001), which was reduced over time, and substantially induced apoptosis in a IOP-dependent fashion (p < 0.001). Ocular hypertensive retinas with DM had significantly more TUNEL positive cells than those without DM despite of the similar time course of IOP changes (p < 0.001).


CONCLUSIONS
DM has an additive effect on apoptosis induction by chronic elevation of IOP. Diabetes may act as a risk factor of open-angle glaucoma by increasing susceptibility of retinal cells including retinal ganglion cells to apoptosis triggered by additional stresses such as elevated IOP.
Kanamori
Akiyasu
A
Department of Organ Therapeutics, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan.
Nakamura
Makoto
M
Mukuno
Hirokazu
H
Maeda
Hidetaka
H
Negi
Akira
A
D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D007429:Intraocular Pressure; D008297:Male; D009457:Neuroglia / Q000473:pathology*; D009798:Ocular Hypertension / Q000150:complications / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology*
D001786:Blood Glucose