Nonessential role of beta3 and beta5 integrin subunits for efficient clearance of cellular debris after light-induced photoreceptor degeneration.
OBJECTIVE
During light-induced photoreceptor degeneration, large amounts of cellular debris are formed that must be cleared from the subretinal space. The integrins alphavbeta5 and alphavbeta3 are involved in the normal physiological process of phagocytosis in the retina. This study was conducted to investigate the question of whether the lack of beta5 and/or beta3 integrin subunits might influence the course of retinal degeneration and/or clearance of photoreceptor debris induced by acute exposure to light.


METHODS
Wild-type, beta5(-/-) and beta3(-/-) single-knockout, and beta3(-/-)/beta5(-/-) Ccl2(-/-)/beta5(-/-) double-knockout mice were exposed to 13,000 lux of white light for 2 hours to induce severe photoreceptor degeneration. Real-time PCR and Western blot analysis were used to analyze gene and protein expression, light- and electron microscopy to judge retinal morphology, and immunofluorescence to study retinal distribution of proteins.


RESULTS
Individual or combined deletion of beta3 and beta5 integrin subunits did not affect the pattern of photoreceptor cell loss or the clearance of photoreceptor debris in mice compared with that in wild-type mice. Invading macrophages may contribute to efficient phagocytosis. However, ablation of the MCP-1 gene did not prevent macrophage recruitment. Several chemokines in addition to MCP-1 were induced after light-induced damage that may have compensated for the deletion of MCP-1.


CONCLUSIONS
Acute clearance of a large amount of cellular debris from the subretinal space involves invading macrophages and does not depend on beta3 and beta5 integrins.
Joly
Sandrine
S
Department of Ophthalmology, Laboratory for Retinal Cell Biology, Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland. sandrine.joly@usz.ch
Samardzija
Marijana
M
Wenzel
Andreas
A
Thiersch
Markus
M
Grimm
Christian
C
D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D003623:Dark Adaptation; D019084:Fluorescent Antibody Technique, Indirect; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039641:Integrin beta Chains / Q000502:physiology*; D039661:Integrin beta3 / Q000502:physiology*; D008027:Light; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D039641:Integrin beta Chains; D039661:Integrin beta3; C084344:integrin beta5; D051416:Focal Adhesion Protein-Tyrosine Kinases