RESUMEN
The results of the investigations of photoaggregation of the main eye lens proteins alpha-, beta- and gamma-crystallins and the model protein carbonic anhydrase in response to pulsed irradiation by a XeCI laser at 308 nm in the wide range of pulse energy densities (w) and pulse repetition rates (F) have been reviewed. A nonlinear dependence of aggregation efficiency on the values of w, F, and the concentration of protein solution was found. A theoretical model that qualitatively describes the experimental results was developed. The aggregation of N-amino-arm truncated beta A3-crystallin was analyzed. It was found that the loss of the N-amino-arm as a result of mutation or eye lens aging increases the probability of UV-induced beta-crystallin aggregation, thereby increasing the predisposition of eye lens to senile cataract. The influence of some short-chain peptides on the aggregation efficiency of beta-crystallin and beta-crystallin in solution with alpha-crystallin was investigated. Based on the results obtained, a combination of peptides (called "a new preparation") was found that most effectively delays the crystallin aggregation. The preparation has been probed on experimental animals. The trials showed that the preparation increases the delay in the development of UV-induced cataract in rats. The possibility of designing a drug for the prophylaxis of the development of cataract in humans based on this preparation is discussed.
Asunto(s)
Cristalinas/química , Rayos Láser , Modelos Químicos , Péptidos/química , Rayos Ultravioleta , Animales , Catarata/etiología , Catarata/genética , Catarata/prevención & control , Cristalinas/genética , Humanos , Cristalino/química , Mutación , Péptidos/uso terapéutico , Ratas , Rayos Ultravioleta/efectos adversosRESUMEN
UV-induced aggregation of betaL-crystallin, one of the major lens proteins, was studied under its pulse radiation with XeCl laser at a wavelength of 308 nm. Unlike the in vitro tested dipeptides L-carnosine, N-acetyl carnosine, D-panthetine, and particularly their combination, the so-called new chaperon was demonstrated to slow down the rate of photoaggregatin of beta-crystallin. The new chaperon, a mixture of D-pathethine and N-acetyl carnosine was ascertained to protect a mixture of betaL- and alpha-crystallins from UV-induced aggregation to a greater extent than D-pathethine or N-acetyl carnosine used alone. An effective drug based on the new chaperon may be designed for the prevention of cataract in sight.
Asunto(s)
Carnosina/análogos & derivados , Catarata/tratamiento farmacológico , Láseres de Excímeros/efectos adversos , Cristalino/metabolismo , Chaperonas Moleculares/uso terapéutico , Rayos Ultravioleta/efectos adversos , beta-Cristalinas/metabolismo , Carnosina/uso terapéutico , Catarata/etiología , Catarata/metabolismo , Quimioterapia Combinada , Humanos , Cristalino/efectos de los fármacos , Cristalino/efectos de la radiación , beta-Cristalinas/efectos de los fármacos , beta-Cristalinas/efectos de la radiaciónRESUMEN
There is a potential of therapeutic action on certain stages of caractogenesis, in particular on the aggregation of water-soluble proteins of cytoplasmic lens fiber cells, giving rise to insoluble protein complexes. The effect of a combined preparation (N-acetyl carnosine and D-patethine), acting by the chaperon-like mechanism, was studied in vivo on a prolonged rat model of UV-induced cataract. The use of the combined preparation consisting of a mixture of peptides of N-acetyl carnosine and D-patethine in a ratio of 1:1 as ocular instillations and intraperitoneal injections could slow down the development of UV-induced cataract in vivo. Pathomorphological studies suggest that the combined preparation has a protective effect on lens tissue when the rat model of UV-induced cataract is employed.