Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration.
OBJECTIVE
Subretinal fibrosis causes damage to visual acuity, especially if the lesion is in the macula, as is frequently observed in advanced age-related macular degeneration. Exudate leukocytes form abnormal vessels that initiate regional inflammation accompanied with local glial proliferation and matrix production. The purpose of this study was to establish an animal model of focal subretinal fibrosis.


METHODS
Macrophage-rich peritoneal exudate cells (PECs) were injected into the subretinal space of C57BL/6 or MCP-1 knockout (KO) mice. Seven days later, the size of the subretinal fibrotic tissue was evaluated by the adherent area of glial fibrillary acidic protein (GFAP)-positive retinal glial cells on choroidal flat mounts. Myofibroblastic changes and collagen synthesis were detected by α-smooth muscle actin (α-SMA) and Masson trichrome staining of the histologic section, respectively. α-SMA expression was also examined on retinal pigment epithelium (RPE) cells during co-culture with activated macrophages.


RESULTS
Subretinal fibrous tissue was observed by funduscopy in PEC-injected mice after 7 days. The tissue consisted of a monotonous, low-cell-density area that expressed α-SMA with collagen synthesis. Both steroid and antioxidant treatment can reduce residual glia. Because PEC-injected MCP-1 KO mice showed less residual glia, not only exogenous macrophages, but also intrinsic macrophages were activated. The macrophages directly induced myofibrotic changes in RPE cells in vitro.


CONCLUSIONS
Activated macrophages form subretinal fibrosis when they are placed in the subretinal space and induce myofibrotic changes in RPE cells.
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka, Japan.
Young-Joon
YJ
Jo
Koh-Hei
KH
Sonoda
Yuji
Y
Oshima
Atsunobu
A
Takeda
Ri-ichiro
R
Kohno
Jun
J
Yamada
Junji
J
Hamuro
Yang
Y
Yang
Shoji
S
Notomi
Toshio
T
Hisatomi
Tatsuro
T
Ishibashi
D000199:Actins / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D008262:Macrophage Activation; D008268:Macular Degeneration / Q000175:diagnosis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009898:Optic Disk / Q000473:pathology; D012160:Retina / Q000473:pathology*
C558396:Acta2 protein, mouse; D000199:Actins; D003094:Collagen