Expression and role of VEGF--a in the ciliary body.
OBJECTIVE
The role of VEGF-A in the normal ciliary body is largely unexplored. The ciliary body is similar in many respects to the choroid plexus of the brain, and we demonstrated previously the importance of VEGF-A in maintenance of choroid plexus vasculature and ependymal cells. Therefore, the role of VEGF-A in ciliary body homeostasis was explored.


METHODS
Swiss-Webster mice (VEGF-LacZ) were used to determine VEGF-A expression during ciliary body development and in the adult. VEGFR2 expression was determined in adult wild type C56BL/6J mice. Systemic VEGF-A neutralization in vivo was achieved with adenovirus-mediated overexpression of soluble VEGFR1 (sFlt1). Following VEGF-A neutralization, the ciliary epithelium was analyzed by light microscopy and transmission electron microscopy (TEM). The effect of VEGF-A blockade on ciliary body function also was assessed by measuring intraocular pressure.


RESULTS
VEGF-A expression was detected at embryonic day 18.5 (E18.5), the onset of ciliary process formation. In the adult ciliary body, VEGF-A was expressed by the pigmented epithelium, whereas VEGFR2 was localized primarily to the capillary endothelium and nonpigmented epithelium. Systemic VEGF-A neutralization led to a thinning of the nonpigmented epithelium, vacuolization of the pigmented epithelium, loss of capillary fenestrations, and thrombosis. These changes were associated with impaired ciliary body function, as evidenced by decreased intraocular pressure in sFlt1-overexpressing animals (15.31 ± 2.06 mm Hg) relative to controls (18.69 ± 1.49 mm Hg).


CONCLUSIONS
VEGF-A has an important role in ciliary body homeostasis. Potential for undesired off-target effects should be considered with the chronic use of anti-VEGF-A therapies.
Schepens Eye Research Institute/Massachusetts Eye and Ear, Boston, Massachusetts 02114, USA.
Knatokie M
KM
Ford
Magali
M
Saint-Geniez
Tony E
TE
Walshe
Patricia A
PA
D'Amore
D000818:Animals; D002924:Ciliary Body / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D017348:Microscopy, Electron, Scanning Transmission; D011247:Pregnancy; D011270:Pregnancy, Animal; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D042461:Vascular Endothelial Growth Factor A