title: p53 selectively regulates developmental apoptosis of rod photoreceptors.
abstract: Retinal cells become post-mitotic early during post-natal development. It is likely that p53, a well-known cell cycle regulator, is involved in regulating the genesis, differentiation and death of retinal cells. Furthermore, retinal cells are under constant oxidative stress that can result in DNA damage, due to the extremely high level of metabolic activity associated with phototransduction. If not repaired, this damage may result in p53-dependent cell death and ensuing vision loss. In this study, the role of p53 during retinal development and in the post-mitotic retina is investigated. A previously described super p53 transgenic mouse that expresses an extra copy of the mouse p53 gene driven by its endogenous promoter is utilized. Another transgenic mouse (HIP) that expresses the p53 gene in rod and cone photoreceptors driven by the human interphotoreceptor retinoid binding protein promoter was generated. The electroretinogram (ERG) of the super p53 mouse exhibited reduced rod-driven scotopic a and b wave and cone-driven photopic b wave responses. This deficit resulted from a reduced number of rod photoreceptors and inner nuclear layer cells. However, the reduced photopic signal arose only from lost inner retinal neurons, as cone numbers did not change. Furthermore, cell loss was non-progressive and resulted from increased apoptosis during retinal developmental as determined by TUNEL staining. In contrast, the continuous and specific expression of p53 in rod and cone photoreceptors in the mature retinas of HIP mice led to the selective loss of both rods and cones. These findings strongly support a role for p53 in regulating developmental apoptosis in the retina and suggest a potential role, either direct or indirect, for p53 in the degenerative photoreceptor loss associated with human blinding disorders.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Vuong
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Brobst
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivanovic
authors.forename: David M
authors.initials: DM
authors.lastname: Sherry
authors.forename: Muayyad R
authors.initials: MR
authors.lastname: Al-Ubaidi
mesh_terms: D000818:Animals; D017209:Apoptosis; D048430:Cell Shape; D002478:Cells, Cultured; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53