A novel function of p53: a gatekeeper of retinal detachment.
Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor α-mediated contraction of cells in a collagen gel and retinal detachment in an animal model of PVR). Furthermore, preventing the decline in the level of p53 with agents such as Nutlin-3 protected from retinal detachment, which is the most vision-compromising component of PVR. Finally, Nutlin-3 may be effective in the clinical setting because it prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane. These studies identify Nutlin-3 as a potential PVR prophylaxis.
The Schepens Eye Research Institute, Boston, Massachusetts, USA.
Hetian
H
Lei
Marc-Andre
MA
Rheaume
Jing
J
Cui
Shizuo
S
Mukai
David
D
Maberley
Arif
A
Samad
Joanne
J
Matsubara
Andrius
A
Kazlauskas
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003228:Conjunctiva / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D010879:Piperazines / Q000494:pharmacology; D011817:Rabbits; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012163:Retinal Detachment / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D007093:Imidazoles; D010879:Piperazines; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3; D003094:Collagen; D020796:Receptor, Platelet-Derived Growth Factor alpha