Age-dependent rat retinal ganglion cell susceptibility to apoptotic stimuli: implications for glaucoma

• Published in: Clinical & experimental ophthalmology 2011-04, Vol.39 (3), p.243-251
• Main Authors: Guerin, Marc B, Donovan, Maryanne, McKernan, Declan P, O'Brien, Colm J, Cotter, Thomas G
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Animals, Newborn; apoptosis; Apoptosis - drug effects; Apoptotic Protease-Activating Factor 1 - metabolism; Blotting, Western; Calcimycin - toxicity; Caspase 3 - metabolism; Cells, Cultured; development; Disease Susceptibility; Fluorescent Antibody Technique, Indirect; Glaucoma; Glaucoma - etiology; Glaucoma - pathology; In Situ Nick-End Labeling; Nerve Growth Factors - physiology; neurotrophin; Rats; Rats, Sprague-Dawley; Retina; retinal ganglion cell; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Rodents
• ISSN: 1442-6404; 1442-9071
• DOI: 10.1111/j.1442-9071.2011.02496.x

Background:  This paper seeks to investigate differences between the neonatal and adult retinal ganglion cell populations to apoptotic death stimuli. Design and Samples:  In vitro and ex vivo paradigms involving P6 and P60 Sprague–Dawley rat retinal explants and retinal ganglion cells were employed. Methods:  Postnatal day 6 (P6) and 60 (P60) Sprague–Dawley retinal ganglion cells and retinal explants were either serum starved or subjected to excitotoxicity using calcium ionophore A23187. Main Outcome Measures:  Apoptosis was detected in both models using terminal dUTP nick end labelling. Expression of Apaf‐1, active caspases‐3 and 9 in P6 and P60 retinas, and in the ganglion cell layer was examined using Western blotting. Results:  In both the dissociated retinal ganglion cell and retinal explant models, P60 retinal ganglion cells were significantly less susceptible to excitoxicity and serum starvation than their P6 counterparts. Western blotting indicated that active caspase‐3 and Apaf‐1 are downregulated in the Sprague–Dawley rat retina at P60 compared with P6 Conclusions:  We demonstrate that neonatal Sprague–Dawley retinal ganglion cells are more susceptible to glaucoma‐related death stimuli than their adult counterparts in dissociated retinal ganglion cells and axotomized retinal explant models. It is apparent that these different retinal ganglion cell populations are inherently designed to react differently to death stimuli. Thus caution should be exercised when noting the high susceptibility of neonatal retinal ganglion cells to glaucomatous death stimuli.