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Targeting long non-coding RNA MALAT1 alleviates retinal neurodegeneration in diabetic mice
Yu-Lan Zhang1, Han-Ying Hu1, Zhi-Peng You1
1Department of Ophthalmology, the Second Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China.
Aim:
To observe the effect of inhibiting long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on diabetic neurodegeneration.
Methods:
Thirty-six 8-week-old C57BL/6 mice were randomly divided into normal control, diabetic control, diabetic scrambled small interfering RNAs (siRNAs) and diabetic MALAT1-siRNA groups. After diabetic induction with streptozocin intraperitoneally-injection, the diabetic MALAT1-siRNA group was intravitreally injected with 1 µL 20 µmol/L MALAT1 siRNA, and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA. Electroretinography was performed to examine photoreceptor functions 16wk after diabetes induction. MALAT1 expression was detected via real time polymerase chain reaction. Cone morphological changes were examined using immunofluorescence. Rod morphological changes were examined by determining outer nuclear layer (ONL) thickness.
Results:
The upregulation of retinal MALAT1 expression was detected in the diabetic control mice, while MALAT1 expression in the diabetic MALAT1-siRNA mice was decreased by 91.48% compared to diabetic control mice. The diabetic MALAT1-siRNA and diabetic control mice showed lower a-wave and b-wave amplitudes than did the normal control mice in scotopic and photopic electroretinogram, while the diabetic MALAT1-siRNA mice showed higher amplitudes than diabetic control mice. Morphological examination revealed that ONL thickness in the diabetic MALAT1-siRNA and diabetic control mice was lower than normal control mice. However, ONL thickness was greater in the diabetic MALAT1-siRNA mice than diabetic control mice. Moreover, the diabetic control mice performed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA mice.
Conclusion:
Inhibiting retinal MALAT1 results in mitigative effects on the retinal photoreceptors, thus alleviating diabetic neurodegeneration.
Insights
Inhibiting the long non-coding RNA MALAT1 in diabetic mice protected retinal photoreceptors. This suggests MALAT1 inhibition may alleviate diabetic neurodegeneration and preserve vision.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Diabetic neurodegeneration poses a significant threat to vision.
- Long non-coding RNAs (lncRNAs) are implicated in various cellular processes, including neurodegeneration.
- Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA with potential roles in diabetic complications.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting MALAT1 in diabetic retinopathy.
- To determine the effect of MALAT1 knockdown on retinal photoreceptor function and morphology in a mouse model of diabetes.
Main Methods:
- A mouse model of diabetes was established using streptozotocin injection.
- Diabetic mice received intravitreal injections of MALAT1-specific small interfering RNAs (siRNAs) or scrambled siRNAs.
- Photoreceptor function was assessed using electroretinography (ERG).
- Retinal structure was evaluated by examining cone and rod morphology, including outer nuclear layer (ONL) thickness.
Main Results:
- Retinal MALAT1 expression was significantly upregulated in diabetic mice.
- MALAT1 inhibition via siRNA reduced MALAT1 expression by over 90% in diabetic retinas.
- ERG recordings showed that MALAT1 inhibition partially preserved a-wave and b-wave amplitudes compared to diabetic controls.
- Histological analysis revealed that MALAT1 inhibition increased ONL thickness and improved cone cell arrangement and outer segment length.
Conclusions:
- Inhibition of MALAT1 demonstrates a protective effect on retinal photoreceptors in diabetic mice.
- Targeting MALAT1 may represent a novel therapeutic strategy for alleviating diabetic neurodegeneration and preserving vision.
