Diabetes exacerbates retinal oxidative stress, inflammation, and microvascular degeneration in spontaneously hypertensive rats.
OBJECTIVE
Hypertension and diabetes are known risk factors for retinal microvascular damage. However, the combined effects of diabetes with early and established stages of hypertension on retinal microvascular degeneration remain incompletely understood.


METHODS
Male spontaneously hypertensive rats (SHR) were compared to SHR with streptozotocin-induced diabetes (SHR+D) for 6 or 10 weeks and Wistar rats as controls.


RESULTS
Hypertension alone (the SHR group) or in combination with diabetes (the SHR+D group) for 6 weeks induced additive increases in total retinal cell death, compared to the Wistar controls. This increase was associated with significant increases in phosphorylated-Jun N-terminal kinase (pJNK) activation, phosphorylated-Akt inhibition, plasma and retinal lipid peroxides, and soluble intracellular adhesion molecule-1 (sICAM-1) levels. After 10 weeks, a similar trend was still observed in retinal nitrotyrosine, nuclear factor kappaB p65, and tumor necrosis factor-α expression, associated with exacerbated pJNK activation and formation of acellular capillaries.


CONCLUSIONS
In conclusion, combining diabetes and hypertension-potentiated retinal oxidative/inflammatory stress promoted imbalance between the JNK stress and survival Akt pathways resulting in accelerated retinal cell death and acellular capillary formation.
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA.
Islam N
IN
Mohamed
Sahar A
SA
Soliman
Ahmed
A
Alhusban
Suraporn
S
Matragoon
Bindu A
BA
Pillai
Ahmed A
AA
Elmarkaby
Azza B
AB
El-Remessy
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D051057:Proto-Oncogene Proteins c-akt; D048670:MAP Kinase Kinase 4