Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa
Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa
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DOI：
10.1002/jcp.21152
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发表时间：
2007-12-01
影响因子：
5.6
通讯作者：
Campochiaro, Peter A.
中科院分区：
文献类型：
--
作者：
Komeima, Keiichi;Rogers, Brian S.;Campochiaro, Peter A.
视网膜色素变性（RP）是一组异质性疾病，其中多种突变中的一种选择性地导致视杆细胞死亡。视杆细胞死亡后，视锥细胞逐渐死亡，导致失明。抗氧化剂减少rdl/rdl小鼠中的视锥细胞死亡，表明视锥细胞死于快速进展性RP模型中的氧化损伤。在这项研究中，我们试图确定这一观察结果是否可以推广到其他类型的RP模型，rdl 0/rdl 0小鼠，一种更缓慢进行的隐性RP模型，和Q344 ter小鼠，一种快速进行的显性RP模型。与适当的媒介物处理的对照相比，在P18和P35之间用先前发现在rdl/rdl小鼠中有效的抗氧化剂的混合物处理的rdl 0/rdl 0和Q344 ter小鼠显示出显著更高的视锥细胞存活。抗氧化剂处理的rdlO/rdlO小鼠显示出视锥细胞功能的保留，如明视ERG b波振幅的显著增加所示，并且令人惊讶地显示出暗视a波振幅的暂时保留、延长的视杆细胞存活和视紫红质mRNA的减缓的消耗。这些数据表明，氧化损伤有助于视锥细胞死亡，而不管导致视杆细胞死亡的疾病引起的突变，并且在更缓慢进行的视杆细胞变性中，氧化损伤也可能导致视杆细胞死亡。防止氧化损伤可能是RP中广泛适用的治疗策略。
Retinitis pigmentosa (RP) is a heterogeneous group of diseases in which one of a wide variety of mutations selectively causes rod photoreceptor cell death. After rods die, cone photoreceptors gradually die resulting in blindness. Antioxidants reduce cone cell death in rdl/rdl mice indicating that cones die from oxidative damage in that model of rapidly progressive RP. In this study, we sought to determine if this observation could be generalized to models of other types of RP, rdl0/rdl0 mice, a model of more slowly progressive recessive RP, and Q344ter mice, a model of rapidly progressive dominant RP. Compared to appropriate vehicle-treated controls, rdl0/rdl0 and Q344ter mice treated between P18 and P35 with a mixture of antioxidants previously found to be effective in rdl/rdl mice showed significantly greater cone survival. Antioxidant-treated rd10/rdl0 mice showed preservation of cone function as shown by a significant increase in photopic ERG b-wave amplitudes, and surprisingly showed temporary preservation of scotopic a-wave amplitudes, prolonged rod survival, and slowed depletion of rhodopsin mRNA. These data suggest that oxidative damage contributes to cone cell death regardless of the disease causing mutation that leads to the demise of rods, and that in more slowly progressive rod degenerations, oxidative damage may also contribute to rod cell death. Protection from oxidative damage may be a broadly applicable treatment strategy in RP.