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Updated: Jun 7, 2025
Application of Optical Coherence Tomography to a Mouse Model of Retinopathy
Published on: January 12, 2022
Lack of retinal degeneration in a Dram2 knockout mouse model
Kuanxiang Sun1, Junyao Chen2, Yudi Fan2
1The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Qinghai Tibet Plateau Biological Resources, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810008, China.
Abstract:
Damage-regulated autophagy modulator 2 (DRAM2) is a homologue of the DRAM family protein, which can induce autophagy process. In the retina, DRAM2 is located to the inner segment of photoreceptors, the apical surface of retinal pigment epithelial (RPE) cells, and the lysosome. Pathogenic variants of DRAM2 lead to autosomal recessive Cone-rod dystrophy 21 (CORD21). Cone-rod dystrophy is characterised by primary cone involvement, or sometimes simultaneous cone and rod loss, thus leading to decreased visual acuity, colour vision deficits, photophobia, and decreased sensitivity of the central visual field. However, the mechanisms underlying DRAM2 related retinal diseases remained unclear. To further explore the role of Dram2 in the retina, we generated Dram2 knockout mice (KO) by CRISPR/Cas-9 technology and demonstrated that expression of DRAM2 was abolished in KO retinas. Dram2 ablation failed to manifest any retinal degenerative phenotypes. Dram2 KO did not exhibit visible defect in photo response and the overt structure of the retinas. Immunostaing analysis using antibodies against cone opsins revealed no detectable loss of cone cells. Moreover, no visible change was observed in the expression and localisation of rhodopsin and other membrane disc proteins in Dram2 KO retinas and no gliosis and apoptosis were detected in KO mice. In summary, these data revealed lack of overt retinal degeneration in Dram2 KO model and emphasized the importance of further investigation of the mechanisms underlying Cone-rod dystrophy 21.
Insights
Damage-regulated autophagy modulator 2 (DRAM2) is crucial for retinal function. However, DRAM2 knockout mice showed no signs of retinal degeneration, suggesting further research is needed for Cone-rod dystrophy 21.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Damage-regulated autophagy modulator 2 (DRAM2) induces autophagy and is found in retinal cells.
- Pathogenic variants in DRAM2 cause autosomal recessive Cone-rod dystrophy 21 (CORD21), a condition affecting vision.
- The precise mechanisms of DRAM2 in retinal diseases are not fully understood.
Purpose of the Study:
- To investigate the role of Dram2 in the retina.
- To determine if Dram2 deficiency leads to retinal degeneration.
Main Methods:
- Generated Dram2 knockout (KO) mice using CRISPR/Cas-9 technology.
- Assessed retinal structure, photoreceptor function, and cell survival in KO mice.
- Utilized immunofluorescence staining for cone opsins, rhodopsin, and other retinal markers.
Main Results:
- Dram2 expression was successfully abolished in KO retinas.
- Dram2 ablation did not result in any observable retinal degenerative phenotypes.
- No defects in photoreceptor response, retinal structure, cone cell loss, or expression of key retinal proteins were detected.
- Absence of gliosis and apoptosis in KO mice.
Conclusions:
- The study demonstrates a lack of overt retinal degeneration in the Dram2 KO mouse model.
- Further investigation is required to elucidate the mechanisms underlying Cone-rod dystrophy 21.
