Macrophages acquire fibroblast characteristics in a rat model of proliferative vitreoretinopathy.
OBJECTIVE
Our aim was to establish a rat model of proliferative vitreoretinopathy (PVR) induced by macrophages and investigate whether macrophages can be a cell origin of fibroblast-like cells present in PVR.


METHODS
One eye of each rat received an intravitreal injection of macrophages. Clinical examination was performed to evaluate the development of PVR. Histological study was carried out to observe the pathological progression. Immunohistochemical staining with vimentin (VIM), glial fibrillary acidic protein (GFAP), α-smooth-muscle actin (α-SM actin), cytokeratin (CK) and CD68 characterized the cell types within the PVR membranes. The distribution, morphological change of prelabeled macrophages, as well as their colocalization with CD68, VIM, GFAP, α-SM actin and CK, were observed on days 3, 14 and 28 after injection.


RESULTS
In response to intravitreal injection of macrophages, 90% of the experimental rats developed PVR from postoperative day 7. The histological progression of PVR was characterized by the sequential appearance of inflammatory cell invasion, fibroblast proliferation and scar formation. The dominating cells comprising the proliferative membranes at the advanced stage were fibroblasts. Injected macrophages retained round shape and positive staining with CD68 on day 3. On day 28, they acquired elongated/spindle shape combined with intense staining of VIM but absence of CD68, GFAP, α-SM actin and CK, and became the primary constituent of fibrocellular membranes.


CONCLUSIONS
Macrophages effectively and reproducibly induce the development of proliferative fibrocellular membranes in rats. In this PVR model, macrophages acquire fibroblast-like cell phenotype and contribute to fibrocellular membranes directly, suggesting that macrophages may be a cell origin of fibroblast-like cells involved in PVR.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Miao-li
ML
Lin
Yong-ping
YP
Li
Zhan-rong
ZR
Li
Jian-xian
JX
Lin
Xiao-lai
XL
Zhou
Dan
D
Liang
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D054338:Cell Transdifferentiation / Q000502:physiology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D058449:Intravitreal Injections; D007633:Keratins / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000473:pathology*; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D007633:Keratins; D014746:Vimentin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C498862:Acta2 protein, rat