Expression of antiapoptotic and proapoptotic molecules in diabetic retinas.
OBJECTIVE
To investigate the expression of the antiapoptotic and proapoptotic markers in diabetic retinas.


METHODS
In total, 12 donor eyes from six subjects with diabetes mellitus, and 10 eyes from five nondiabetic subjects without known ocular disease serving as control subjects were examined. Immunohistochemical techniques were used with antibodies directed against cyclooxygenase-2 (Cox-2), Akt (protein kinase B), Mcl-1, Bad, cytochrome c, apoptosis-inducing factor (AIF), tumour necrosis factor receptor-1-associated death domain protein (TRADD), and Fas-associated death domain protein (FADD).


RESULTS
In retinas from all subjects without diabetes, cytoplasmic immunoreactivity for the antiapoptotic molecules Cox-2, Akt, and Mcl-1 was noted in ganglion cells. Cytoplasmic immunostaining for Cox-2 was also noted in the retinal pigment epithelial cells. Weak immunoreactivity for the mitochondrial apoptogenic proteins cytochrome c, and AIF was noted in the inner segments of photoreceptors, in the inner one-third of the outer plexiform layer, in cells in the inner nuclear layer, in the inner plexiform layer, and in ganglion cells. There was no immunoreactivity for the other antibodies tested. All diabetic retinas showed de novocytoplasmic immunoreactivity for Bad in ganglion cells, and in occasional cells in the inner nuclear layer. Upregulation of cytochrome cand AIF immunoreactivity was noted. Cox-2, Akt, and Mcl-1 immunoreactivity was not altered in the diabetic retinas. There was no immunoreactivity for TRADD, and FADD.


CONCLUSIONS
Ganglion cells in diabetic and nondiabetic retinas express the antiapoptotic molecules Cox-2, Akt, and Mcl-1. Retinal ganglion cells express the proapoptotic molecule Bad in response to diabetes-induced neuronal injury. Diabetic retinas show upregulation of the mitochondrial proteins cytochrome c, and AIF.
Abu El-Asrar
A M
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Dralands
L
L
Missotten
L
L
Geboes
K
K
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology*; D053200:Fas-Associated Death Domain Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012160:Retina / Q000378:metabolism / Q000503:physiopathology*; D053199:TNF Receptor-Associated Death Domain Protein / Q000032:analysis; D051025:bcl-Associated Death Protein / Q000032:analysis
D051033:Apoptosis Inducing Factor; D015415:Biomarkers; D053200:Fas-Associated Death Domain Protein; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053199:TNF Receptor-Associated Death Domain Protein; D051025:bcl-Associated Death Protein; D045304:Cytochromes c; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt