An Homology Modeling Study of the Retinitis Pigmentosa Genetical Causes and Oxidative Stress

Abstract

Abstract: : Purpose: To analyze the changes induced in the geometry and energetic of the retinal site by single point mutations in the retinal pocket nearest and the possible implications of those abnormalities in the RP disease related with oxidative stress changes. Methods: An amino acid sequence of the Human Rodopsin (HR) containing the retinal site was selected for homology modeling.A search for homologous using BLAST was conducted in the GENBANK and in the Brookhaven Protein Databank.The homology model was built using ProMod.From patients with RP to study oxidative stress biochemistry: Oxidized Proteins,TBARS, Enzymatic activity: Cu-Zn, SOD,Catalase, PhospholipaseA, Xantine-Oxidoreductase, Antioxidant capacity. Results: The region analyzed can produce important changes in the retinal environment when an amino acid is changed for another.All mutations analyzed ,except Lysine mutations, can produce an unhappy photoreaction of isomerization, and therefore a dysfunctional receptor.Besides, the displacement of the retinal could help to produce reactive species at the same time through a photoreaction some of these species activate the caspase cascade driving the cell to apoptosis.Reactive oxygen species generated could be the cause of the photoreceptor death. Conclusions: The effect caused for these mutations in two forms,both the lack of stimulation and the reactive species, probably generated could be the cause of the photoreceptor death in RP.

Keywords: retinal degenerations: hereditary • stress response • photoreceptors