Retinal neovascularization induced by mutant Vldlr gene inhibited in an inherited retinitis pigmentosa mouse model: an in-vivo study
Authors:   Department of Ophthalmology, the 900th Hospital of Joint Logistic Support Forceo of PLA (Clinical Medical College of Fujian Medical University, Dongfang Hopsital Affiliated to Xiamen University), Fuzhou 350025, Fujian Province, China; Center of Clinical Aerospace Medicine, Air Force Medical University, Xi&#x2019;an 710032, Shaanxi Province, China, Yan Wei-Ming , Chen Mei-Zhu ,   Department of Ophthalmology, the 900th Hospital of Joint Logistic Support Forceo of PLA (Clinical Medical College of Fujian Medical University, Dongfang Hopsital Affiliated to Xiamen University), Fuzhou 350025, Fujian Province, China, Wei Dong-Yu ,   Center of Clinical Aerospace Medicine, Air Force Medical University, Xi&#x2019;an 710032, Shaanxi Province, China, Wang Jian-Cong ,   BeiJing HealthOLight Technology Co., Ltd., Beijing 10010, China, Zhang Zuo-Ming ,   Center of Clinical Aerospace Medicine, Air Force Medical University, Xi&#x2019;an 710032, Shaanxi Province, China, Zhang Lei ,   Shaanxi Eye Hospital, Xi&#x2019;an People&#x2019;s Hospital (Xi&#x2019;an Fourth Hospital), Affiliated Guangren Hospital, School of Medicine, Xi&#x2019;an Jiaotong University, Xi&#x2019;an 710004, Shaanxi Province, China, Chen Tao ,   Center of Clinical Aerospace Medicine, Air Force Medical University, Xi&#x2019;an 710032, Shaanxi Province, China
Published: June 2021

AIM: To explore whether the retinal neovascularization (NV) in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa (RP) mouse, which would help to elucidate the possible mechanism and prevention of retinal NV diseases in clinic.
METHODS: The Vldlr-/- mice, the genetic mutant mouse model of retinal NV caused by the homozygous mutation of Vldlr gene, with the rd1 mice, the inherited RP mouse caused by homozygous mutation of Pde6b gene were bred. Intercrossing of the above two mice led to the birth of the F1 hybrids, further inbreeding of which gave birth to the F2 offspring. The ocular genotypes and phenotypes of the mice from all generations were examined, with the F2 offspring grouped according to the genotypes.
RESULTS: The rd1 mice exhibited the RP phenotype of outer retinal degeneration and loss of retinal function. The Vldlr-/- mice exhibited the phenotype of retinal NV obviously shown by the fundus fluorescein angiography. The F1 hydrides, with the heterozygote genotype, exhibited no phenotypes of RP or retinal NV. The F2 offspring with homozygous genotypes were grouped into four subgroups. They were the F2-I mice with the wild-type Pde6b and Vldlr genes (Pde6b+/+-Vldlr+/+), which had normal ocular phenotypes; the F2-II mice with homozygous mutant Vldlr gene (Pde6b+/+-Vldlr-/-), which exhibited the retinal NV phenotype; the F2-III mice with homozygous mutant Pde6b gene (Pde6b-/--Vldlr+/+), which exhibited the RP phenotype. Specifically, the F2-IV mice with homozygous mutant Vldlr and Pde6b gene (Pde6b-/--Vldlr-/-) showed only the RP phenotype, without the signs of retinal NV.
CONCLUSION: The retinal NV can be inhibited by the RP phenotype, which implies the role of a hyperoxic state in treating retinal NV diseases.