The paper provides an interdisciplinary evaluation of the etiology, pathogenesis, and experimental treatments of retinitis pigmentosa (RP). It addresses a 10-year controversy concerning the rate of progression of RP. One laboratory has estimated remaining visual field to be lost at a rate of 4.6% per year, whereas another laboratory estimates loss at 16-18%. This large discrepancy and lack of consensus needs resolution, since they pose serious statistical and operational problems for evaluating experimental treatment approaches to RP. The resolution of the controversy offered in the paper is based on a model of RP in which the initial rate of loss of visual field (the induction phase) is much slower than the subsequent logarithmic first-order rate of loss. The rationale for this kinetic model is that loss of mitochondrial function, possibly due to RP-genetically-related radical processes, has to reach a critical threshold value before the mitochondrial trigger of programmed cell death or apoptosis (i.e., the release of mitochondrial cytochrome c by the opening of the permeability transition pore, PTP) can be activated by an encounter with a second, but kinetically constant causative stress factor - most likely a light-stress-related factor. In its essential (two-causal) aspects, this kinetic model for RP is identical to the kinetic theories that have been proposed for the Gombertz human mortality plot. The described kinetic model for RP provides a solution to the visual field-loss controversy, since the first study was performed with a population containing a greater number of patients in the slow stage of RP than the second. Another objective of the investigation was to identify possible mechanisms of how the numerous genetic mutations in the rods of RP patients could give rise to damaging free-radical reactions capable of triggering apoptosis through their adverse effects on mitochondrial function. Another reason for focusing on radical reactions in RP was to provide a rationale for the proposed use of an extensive array of antioxidants and nutritional supplements for stemming progression of RP. In particular, the investigation focuses on saving cone-dependent central vision, i.e. on saving cells not affected by the genetic problems of the rods, but cells which can become lethally damaged by a spill-over of radicals and related harmful chemical reactions occurring in the rods.The third objective deals with the development of a rationale for a new strategy for retarding RP. This involves the use of desmethyldeprenyl, a metabolite of the anti-Parkinson's drug, deprenyl. The rationale is, in part, based on an observation that desmethyldeprenyl exerts antiapoptotic activities in a variety of neurodegenerative disorders. The protective mechanism involves the overexpression of the anti-apoptotic bcl-2 gene, leading to higher concentrations of bcl-2 proteins, which by binding to mitochondria inhibits the trigger mechanism of apoptosis - the opening of PTP and release of cytochrome C. At the same time, desmethyldeprenyl causes the underexpression of the pro-apoptotic bax gene, which via bax proteins facilitates the opening of the PTP. Both the anti-apoptotic and pro-apoptotic mechanisms appear to be mediated by the binding of desmethyldeprenyl to glyceraldehyde-3-phosphate dehydrogenase. Antiapoptotic effects can also be generated by the parent compound, deprenyl, when this is used daily in low concentrations of 1-2 mg/100 kg body weight. Under these conditions, it appears that the anti-apoptotic metabolite, desmethyldeprenyl, predominates over the pro-apoptotic metabolites of deprenyl, l -methamphetamine and l -amphetamine. Methamphetamine is not formed if desmethyldeprenyl is administered directly and thus could give desmethyldeprenyl a pharmacokinetic advantage over deprenyl. (ABSTRACT TRUNCATED)