Are there obvious reasons for the differences in predicted and actual results? First, we started with the premise that neurotrophins and growth factors are expressed predominantly by Müller glial cells and invading microglial cells (e.g., Valter et al.
29 and Frasson et al.
30 ) and, thus, that changes in expression levels should be measurable in whole retina samples. Although retinal ganglion cells (RGCs) express some of those neurotrophic factors, it was argued that expression levels should not change in these cells because there was no evidence that light damage affects RGCs early in the progression of photoreceptor degeneration. In addition, Müller glial cells outnumber RGCs by a factor of 6,
31 yet the possibility that changes in gene expression in the RGCs might have masked the changes occurring in the Müller glia and the invading microglial cells should not be excluded. Testing this possibility was beyond the scope of this project. Second, Harada et al.
17 examined neurotrophin levels in microglial and Müller glial cells isolated from a 35-day-old rat and cultured for multiple days. Neurotrophin levels under these conditions might differ from the expression profiles of cells within an existing cellular network. Third, the model was established based on juvenile rat retina instead of young adult mouse, which was used here. And finally, fourth, the light paradigms used here and those used by Harada et al.
17 differed. With albino rats, Harada et al.
17 were able to use the continuous light exposure model (24-hour light exposure at approximately 800-1300 lux from postnatal day [P] 22-P35), whereas we used approximately 15-fold brighter light (approximately 15,000 lux) for a shorter period (1.5 hours) followed by 10 days of darkness to allow for the execution of cell death because the BDNF heterozygous mice were on a B6 background (B6.129-BDNF
tm1-LT) and were resistant to continuous light exposure. However, as shown by Hao et al.,
32 the mechanisms differed whereby continuous light exposure and intense light exposure triggered cell death. Both mechanisms required the presence of bleachable rhodopsin; however, intense bright-light damage was independent of the presence of transducin, whereas continuous low-light damage required transducin. Thus, it is plausible that the glial network outlined by Harada et al.
17 is not activated in intense bright light. Unfortunately, none of the growth factors or neurotrophins involved in the glial network have been tested in rescue experiments in the bright-light damage model (summarized in Wenzel et al.
9 ), the results of which might enable greater understanding.