Long Noncoding RNAs as Blood-Based Biomarkers of Diabetic Retinopathy

Area of Science:

• Biochemistry
• Molecular Biology
• Ophthalmology

Background:

• Diabetic retinopathy (DR) prevalence is linked to diabetes duration and hyperglycemia.
• High glucose induces retinal metabolic, molecular, and epigenetic changes before detectable vascular damage.
• Long non-coding RNAs (lncRNAs) are aberrantly expressed in the diabetic retina and are stable in plasma.

Purpose of the Study:

• To investigate the utility of aberrantly expressed retinal lncRNAs as potential biomarkers for diabetic retinopathy.
• To analyze nuclear-encoded (NEAT1, HOTAIR, HOTTIP, MALAT1, H19, Meg3) and mitochondrial-encoded (CytB) lncRNAs.

Main Methods:

• Plasma lncRNA levels were quantified using qRT-PCR in diabetic patients (proliferative DR and no DR) and diabetic rats.
• Results were validated in retinal samples from human donors and diabetic rats.
• Diabetic rat models were studied over two to six months.

Main Results:

• NEAT1, HOTAIR, MALAT1, and HOTTIP were upregulated, while Meg3 and CytB were downregulated in plasma and retina of diabetic patients and rats.
• Abnormal expression of NEAT1 and CytB was detected in rats within two months of diabetes, preceding retinal vascular histopathology.
• Consistent expression patterns for NEAT1 and CytB were observed across human plasma, rat plasma, and rat retina.

Conclusions:

• NEAT1 and CytB exhibit consistent expression patterns in plasma from diabetic patients and in plasma and retina from rodents.
• Plasma NEAT1 and CytB show potential as early, noninvasive biomarkers for detecting retinopathy in diabetic individuals.