Recent developments in our understanding of how platelet-derived growth factor (PDGF) and its receptors contribute to proliferative vitreoretinopathy.
Proliferative vitreoretinopathy, a disease process occurring in the setting of a rhegmatogenous retinal detachment, is thought to develop as a result of exposure of retinal cells to vitreous. Vitreous contains many growth factors, and platelet-derived growth factor (PDGF) has been considered a major contributor to PVR. Evaluation of both PDGF and PDGF receptors (PDGFRs) as potential therapeutic targets in the context of a rabbit model of PVR revealed that PDGFR-based approaches protected from PVR, whereas neutralizing PDGFs was a much less effective strategy. The basis for these observations appears to reflect that fact that the PDGFR could be activated by a wide spectrum of vitreal agents that are outside of the PDGF family. Furthermore, blocking signaling events by which the non-PDGFs indirectly activated PDGF alpha receptor (PDGFRalpha) protected rabbits from developing PVR. These studies demonstrate that the best therapeutic targets for PVR are not PDGFs, but PDGFRalpha and certain signaling events required for indirectly activating PDGFRalpha.
Lei
Hetian
H
The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford St., Boston, MA 02114, USA.
Rheaume
Marc-Andre
MA
Kazlauskas
Andrius
A
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011817:Rabbits; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D012163:Retinal Detachment / Q000150:complications; D015398:Signal Transduction / Q000502:physiology; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control
D010982:Platelet-Derived Growth Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha