Eliminating complement factor D reduces photoreceptor susceptibility to light-induced damage.
OBJECTIVE
Genetic risk factors such as variations in complement factors H (CFH) and B (CFB) have been implicated in the etiology of age-related macular degeneration. It has been hypothesized that inadequate control of complement-driven inflammation may be a major factor in disease pathogenesis. The authors tested the involvement of the complement system in an experimental model for oxidative stress-mediated photoreceptor degeneration, the light-damage mouse model.


METHODS
Changes in gene expression were assessed in BALB/c retinas in response to constant-light (CL) exposure using microarrays and real-time PCR. Susceptibility to CL exposure was tested in CFD(-/-) mice on a BALB/c background. Eyes were analyzed using electrophysiologic and histologic techniques.


RESULTS
Genes encoding for proteins involved in complement activation were significantly upregulated after CL. The altered gene profiles were similar to proteins accumulated in drusen and to genes identified in the retina and RPE/choroid of patients with age-related macular degeneration. Cyclic-light reared CFD(-/-) and CFD(+/+) mice had indistinguishable rod function and number; however, after CL challenge, CFD(-/-) photoreceptors were significantly protected.


CONCLUSIONS
These results suggest that rod degeneration in the CL-damaged retina involves the activity of the alternative complement pathway and that eliminating the alternative pathway is neuroprotective. Thus, the light damage albino mouse model may be a good model to study complement-mediated photoreceptor degeneration.
Rohrer
Bärbel
B
Department of Neurosciences Division of Research, Medical University of South Carolina, Charleston, SC 29425, USA. rohrer@musc.edu
Guo
Yao
Y
Kunchithapautham
Kannan
K
Gilkeson
Gary S
GS
D000818:Animals; D003167:Complement Activation / Q000235:genetics; D011416:Complement Factor D / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000502:physiology; D004596:Electroretinography; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D020419:Photoreceptor Cells, Vertebrate / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D012333:RNA, Messenger; D014157:Transcription Factors; D011416:Complement Factor D; C493491:complement factor D, mouse