Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.
Inherited retinal degeneration (IRD) is a group of fundus diseases characterized by a high degree of genetic heterogeneity and clinical heterogeneity, and more than 300 genetic mutations have been identified in association with IRD. Dysregulation of the intracellular second messenger cyclic guanosine monophosphate (cGMP) plays an important role in the development of IRD. cGMP participates in phototransduction process in photoreceptors. Abnormally elevated cGMP over-activate protein kinase G and cyclic nucleotide-gated channel, causing protein phosphorylation and Ca2+ overload, respectively, and these two cGMP-dependent pathways may individually or collectively drive photoreceptor degenerative lesions and death; therefore, reducing cGMP synthesis and blocking downstream signaling can be considered as treatment strategies. Investigating the molecular mechanisms of cGMP dysregulation in photoreceptor degeneration may provide a more comprehensive picture of the pathogenesis of IRD, as well as ideas for finding new therapeutic targets and designing therapeutic programs.
Objective To observe the changes of inflammatory cytokines in brain protective methods, study the inflammatory mechanism during cerebral protection tissues in different cerebral Methods Eighteen healthy adult dogs were randomly divided into three groups （6 dogs in each group）： normothermic cardiopulmonary bypass （NCPB group）, deep hypothermic circulatory arrest （DHCA group）, and intermittent selective antegrade cerebral perfusion （ISACP） during DHCA（DHCA＋ISACP group）. After operation the water contents in brain tissue were measured ,the hippocampus were removed, and radio-immunity analysis （RIA） was used to measure the content of interleukin-1β（IL-1β） and tumor necrosis factor-alpha （TNF-α） of the hippocampus tissue. The morphology of the hippocampus were examined by transmission electron （TE） microscopy. Results The contents of IL-1β and TNF-α of DHCA group was higher significantly than those of NCPB group and DHCA＋ISACP group （P〈0.01）, there was no significant difference between NCPB group and DHCA＋ISACP group （P〉0.05）. And the contents of TNF-α and IL-1β were positive linear correlated with degree of edema of brain tissues （r = 0. 987, 0.942; P〈 0.01）. TE examination revealed that the damage of the uhrastructure in the DHCA group was more severe than that in NCPB group and DHCA＋ISACP group. Conclusions This experiment revealed that long duration DHCA can bring some damages to the brain and that ISACP during long-term DHCA has brain protective effects to some extent. IL-1β and TNF-α play an effective role in the brain damage of long-term DHCA.