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Retina-specific mRNA in the assessment of diabetic retinopathy
Z Shalchi1, H S Sandhu, A N Butt
1Department of Diabetes and Endocrinology, Guy's and St Thomas' Hospital NHS Trust, London, United Kingdom.
Abstract:
In a previous study we demonstrated the presence and diagnostic usefulness of circulating rhodopsin mRNA in the assessment of diabetic retinopathy (DR). In the present study we investigated three further retina-specific markers in blood to determine their suitability as markers of DR. The markers were RPE65, retinoschisin, and melanopsin. Whole blood was collected from diabetic patients and healthy controls into PAXgene Blood RNA tubes and RNA was extracted using the PAXgene Blood RNA System. Quantitative real-time PCR was used to quantify mRNA for RPE65, retinoschisin, and melanopsin. beta-actin mRNA was used for normalization. RPE65, retinoschisin, and beta-actin mRNA were detected in 100% of subjects; melanopsin was not detected in either controls or diabetic patients. Circulating RPE65 mRNA concentration was 63% higher in diabetic patients than in healthy individuals (P= 0.019), whereas retinoschisin showed no change between the two groups. Compared with healthy controls, circulating RPE65 mRNA concentration was higher in diabetics with no retinopathy (30%; P= NS), background DR (93%; P= 0.01), preproliferative DR (20%; P= NS), and proliferative DR (107%; P= 0.004). Compared with diabetics with no retinopathy, levels of RPE65 mRNA were also significantly higher (60%) in the presence of proliferative DR (P= 0.029). In contrast, levels of retinoschisin mRNA were lower in background DR (34%; P= 0.033), preproliferative DR (43%; P= 0.026), and proliferative DR (47%; P= 0.038) compared to that in diabetics without retinopathy. We conclude that not all retina-specific mRNA species are detectable in circulation (e.g., melanopsin). This may be related to differences in expression levels for the individual markers. Both RPE65 and retinoschisin were detectable and demonstrated contrasting trends in diabetics with and without retinopathy. In combination with rhodopsin, RPE65, and retinoschisin, mRNA may offer a useful tool in developing a blood test for DR.
Insights
New blood markers, RPE65 and retinoschisin mRNA, show promise for diagnosing diabetic retinopathy (DR). RPE65 levels were elevated in diabetic patients, while retinoschisin levels decreased with DR severity, suggesting potential for a non-invasive DR blood test.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a leading cause of blindness.
- Current DR diagnosis relies on invasive eye examinations.
- Circulating cell-free mRNA offers a potential non-invasive diagnostic approach.
Purpose of the Study:
- To investigate the diagnostic utility of circulating RPE65, retinoschisin, and melanopsin mRNA as biomarkers for diabetic retinopathy (DR).
- To compare mRNA levels in diabetic patients with and without DR against healthy controls.
Main Methods:
- Quantitative real-time PCR was used to measure mRNA levels of RPE65, retinoschisin, and melanopsin in whole blood.
- Blood samples were collected from diabetic patients and healthy controls.
- beta-actin mRNA served as the normalization control.
Main Results:
- RPE65 mRNA was detected in all subjects and showed significantly higher concentrations in diabetic patients compared to controls (P=0.019).
- RPE65 mRNA levels correlated positively with DR severity.
- Retinoschisin mRNA levels were lower in patients with varying stages of DR compared to those without retinopathy (P<0.05).
- Melanopsin mRNA was not detected in any subjects.
Conclusions:
- RPE65 and retinoschisin mRNA are detectable in circulation and exhibit distinct patterns in diabetic retinopathy.
- These retina-specific mRNA markers, along with rhodopsin, may contribute to a novel blood-based diagnostic test for DR.
- Melanopsin is not a suitable circulating biomarker for DR, likely due to low expression levels.
