Barbel Rohrer

..We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted" to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD...

..All of these components need to be addressed if rods are to be successfully protected...

..Improving our understanding of the local regulation of this pathway in the eye is essential for developing improved treatment approaches for AMD...

..Our results suggest that both, the classical complement system of innate immunity and a functional acquired immune response are not essential for the degenerative process in the rd1 mouse retina...

..The authors tested the involvement of the complement system in an experimental model for oxidative stress-mediated photoreceptor degeneration, the light-damage mouse model...

..This study was designed to investigate the feasibility of restoring functional cones with exogenous 11-cis retinal...

..These data indicate that there does not appear to be evidence for postsynaptic deficits in glutamatergic signaling in the ON and OFF bipolar cells of mice lacking trkB...

..In both the in vivo and in vitro paradigm of RPE damage, a model requiring molecular events known to be involved in AMD, complement-dependent VEGF production, was confirmed. These data may open new avenues for AMD treatment strategies...

....

..To determine the effects of trkB deficiency in the mouse retina on photoreceptor development and retinal organization, in the absence of confounding systemic effects...

..This project was designed to determine the amount of regenerable opsin in Rpe65-/- mice during development and aging, and to examine the function of this rhodopsin by electroretinography (ERG)...

..CR2-fH consists of the N terminus of mouse fH, which contains the AP-inhibitory domain, linked to a complement receptor 2 (CR2) targeting fragment that binds complement activation products...

..To strengthen our understanding about the role of trkB in rod development by correlating functional and biochemical retinal phenotypes with levels of trkB expression in two independently created trkB transgenic lines...

..Thus, TrkB signaling is not required for survival of RGCs during the period of target-dependent survival, but does appear to reduce degeneration of RGCs in adult animals...

..The authors hypothesized that retinas with reduced BDNF levels in which the BDNF-mediated release of neuroprotective signals is dampened are more susceptible to light-induced photoreceptor degeneration...

..Here, we determine the consequences of 11-cis retinal withdrawal and supplementation on cone development in the all-cone Nrl(-/-) retina...

..Thus, unless the common upstream initiator for a given photoreceptor dystrophy is found, multiple rescue paradigms need to be used to target all active pathways...

..Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein...

..Retinal degeneration (RD) is a complex mechanism that appears to involve many biologic processes including oxidative stress, apoptosis, and cellular remodeling. Currently there are 51 mapped, but not identified, RD human disease loci...

..These results establish a central role for oxidative stress in cGMP-induced cell death and suggest a ROS-mediated sequential activation of signal transduction events, which provide targets for future treatment strategies...

..And third, these results argue that the up-stream regulators of autophagy need to be identified as potential therapeutic targets in photoreceptor degeneration...

..Moreover, inner retinal cells respond to exogenous BDNF with c-fos expression and extracellular signal-regulated kinase phosphorylation. Thus, interactions of rods with TrkB-expressing cells must be required for normal rod development...

....

..Here, we further examined rod and cone development, chromophore production by the RPE, and photoreceptor signaling to the inner retina under organ culture conditions...

..Taken together, identifying how sublytic MAC induces VEGF expression and secretion might offer opportunities to selectively inhibit pathological VEGF release only...

..Taken together, we have defined novel mechanisms of complement activation in oxidatively stressed RPE, linking molecular events involved in age-related macular degeneration, including the presence of natural antibodies and neoepitopes...

..Here, we tested whether complement attack on RPE monolayers changes MMP secretion and activation, thereby altering the availability of growth factors in the extracellular space...

..Our investigation revealed that unless the common upstream initiator for a given photoreceptor dystrophy can be found, multiple rescue paradigms need to be used to target all active pathways...

..These findings suggest that the LC-NE system of Gdnf+/- mice is impaired and suggest that GDNF plays an important role in continued maintenance of this neuronal system throughout life...

..However, more importantly, it will provide avenues for studying gene defects at the single cell level not only in the retina, but in other systems as well. ..

..We expect to isolate common downstream target genes that are activated both during degeneration and neuroprotection. ..

..Our current research suggests that complement inhibitors may be very effective therapeutic agents, as they target proximal events prior to inflammation and CNV. ..