Stromal cell-derived factor-1 is essential for photoreceptor cell protection in retinal detachment.
Stromal cell-derived factor-1 (SDF-1) causes chemotaxis of CXCR4-expressing bone marrow-derived cells. SDF-1 is involved in the pathogenesis of various vascular diseases, including those of the eye. However, the role of SDF-1 in neuronal diseases is not completely understood. Here, we show higher SDF-1 levels in the vitreous humor of patients with retinal detachment (RD) compared with normal patients. SDF-1 correlated positively with the duration as well as the extent of RD. Furthermore, SDF-1 correlated significantly with levels of interleukin-6 and interleukin-8, but not with vascular endothelial growth factor. Western blot analysis results showed significant SDF-1 up-regulation in detached rat retinas compared with normal animals. Immunohistochemistry data showed that SDF-1 was co-localized with the glial cells of the detached retina. SDF-1 blockade with a neutralizing antibody increased photoreceptor cell loss and macrophage accumulation in the subretinal space. The retinal precursor cell line R28 expressed CXCR4. SDF-1 rescued serum starvation-induced apoptosis in R28 cells and enhanced their ability to participate in wound closure in a scratch assay. Our results indicate a surprising, protective role for SDF-1 in RD. This effect may be mediated directly or indirectly through other cell types.
Otsuka
Hiroki
H
Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
Arimura
Noboru
N
Sonoda
Shozo
S
Nakamura
Makoto
M
Hashiguchi
Teruto
T
Maruyama
Ikuro
I
Nakao
Shintaro
S
Hafezi-Moghadam
Ali
A
Sakamoto
Taiji
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010786:Photoreceptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012163:Retinal Detachment / Q000378:metabolism* / Q000473:pathology*; D014822:Vitreous Body / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects
D054377:Chemokine CXCL12; D018925:Chemokines; D016207:Cytokines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D019718:Receptors, CXCR4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3