Improvement of Visual Performance With Intravitreal Administration of 9-cis-Retinal in Rpe65-Mutant Dogs

Em busca de novos métodos de tratamento para a retinose pigmentar causada por mutações na rodopsina.

“…Indeed, addition of 11-cis retinal during the time the protein is being synthesized to the cells prevented misfolding and helped proper trafficking of both mutants expressed in HEK293 cells. These results show the importance of 11-cis retinal in the biosynthesis and trafficking of rodopsin in cells and are in agreement with published results (Gearhart et al, 2010;Krebs et al, 2010;Maeda et al, 2006). The rescue of folded rhodopsin allowed us to carry out a larger number of in-depth biophysical characterizations of the purified mutant proteins than was previously possible.…”

Em busca de novos métodos de tratamento para a retinose pigmentar causada por mutações na rodopsina.

“…Indeed, addition of 11-cis retinal during the time the protein is being synthesized to the cells prevented misfolding and helped proper trafficking of both mutants expressed in HEK293 cells. These results show the importance of 11-cis retinal in the biosynthesis and trafficking of rodopsin in cells and are in agreement with published results (Gearhart et al, 2010;Krebs et al, 2010;Maeda et al, 2006). The rescue of folded rhodopsin allowed us to carry out a larger number of in-depth biophysical characterizations of the purified mutant proteins than was previously possible.…”

Catalytic synthesis of 9- cis -retinoids: mechanistic insights

“…Such quantities allow for large-scale tests of their therapeutic capabilities in retinal degeneration models in murine and canine models as a prelude to human investigations. [62][63][64][65] As we have shown previously, supplementation of 3 mg of 9-cis-retinal 2a in the LCA dog model, which lacks visual cycle function, showed improvement of 25% in photoreceptor function. 62 The presented reaction of all-trans-retinyl acetate 1c that occurs most favorably in the presence of catalyst I yields an exceptional 20% of the desired 9-cis isomer.…”

Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision

“…Treatment with exogenous 9cRAL recovers ERG responses in Rpe65 -/mice and functional vision in Rpe65-deficient dogs, establishing its potential as a chromophore replacement therapy (30,47,48). In agreement, immediate photopic vision significantly improved emixustat and/or fenretinide-treated larvae supplemented with 9cRAL.…”

Em busca de novos métodos de tratamento para a retinose pigmentar causada por mutações na rodopsina.

“…Indeed, addition of 11-cis retinal during the time the protein is being synthesized to the cells prevented misfolding and helped proper trafficking of both mutants expressed in HEK293 cells. These results show the importance of 11-cis retinal in the biosynthesis and trafficking of rodopsin in cells and are in agreement with published results (Gearhart et al, 2010;Krebs et al, 2010;Maeda et al, 2006). The rescue of folded rhodopsin allowed us to carry out a larger number of in-depth biophysical characterizations of the purified mutant proteins than was previously possible.…”

Catalytic synthesis of 9- cis -retinoids: mechanistic insights

“…Such quantities allow for large-scale tests of their therapeutic capabilities in retinal degeneration models in murine and canine models as a prelude to human investigations. [62][63][64][65] As we have shown previously, supplementation of 3 mg of 9-cis-retinal 2a in the LCA dog model, which lacks visual cycle function, showed improvement of 25% in photoreceptor function. 62 The presented reaction of all-trans-retinyl acetate 1c that occurs most favorably in the presence of catalyst I yields an exceptional 20% of the desired 9-cis isomer.…”

Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision

“…Treatment with exogenous 9cRAL recovers ERG responses in Rpe65 -/mice and functional vision in Rpe65-deficient dogs, establishing its potential as a chromophore replacement therapy (30,47,48). In agreement, immediate photopic vision significantly improved emixustat and/or fenretinide-treated larvae supplemented with 9cRAL.…”

Em busca de novos métodos de tratamento para a retinose pigmentar causada por mutações na rodopsina.

“…Indeed, addition of 11-cis retinal during the time the protein is being synthesized to the cells prevented misfolding and helped proper trafficking of both mutants expressed in HEK293 cells. These results show the importance of 11-cis retinal in the biosynthesis and trafficking of rodopsin in cells and are in agreement with published results (Gearhart et al, 2010;Krebs et al, 2010;Maeda et al, 2006). The rescue of folded rhodopsin allowed us to carry out a larger number of in-depth biophysical characterizations of the purified mutant proteins than was previously possible.…”

Catalytic synthesis of 9- cis -retinoids: mechanistic insights

“…Such quantities allow for large-scale tests of their therapeutic capabilities in retinal degeneration models in murine and canine models as a prelude to human investigations. [62][63][64][65] As we have shown previously, supplementation of 3 mg of 9-cis-retinal 2a in the LCA dog model, which lacks visual cycle function, showed improvement of 25% in photoreceptor function. 62 The presented reaction of all-trans-retinyl acetate 1c that occurs most favorably in the presence of catalyst I yields an exceptional 20% of the desired 9-cis isomer.…”

Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision

“…Treatment with exogenous 9cRAL recovers ERG responses in Rpe65 -/mice and functional vision in Rpe65-deficient dogs, establishing its potential as a chromophore replacement therapy (30,47,48). In agreement, immediate photopic vision significantly improved emixustat and/or fenretinide-treated larvae supplemented with 9cRAL.…”