Progressive Thinning of Retinal Nerve Fiber Layer/Ganglion Cell Layer (RNFL/GCL) as Biomarker and Pharmacological
Gianpaolo Zerbini1, Silvia Maestroni1, Ilaria Viganò1
1Complications of Diabetes Unit, Diabetes Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
Abstract:
Diabetes-driven retinal neurodegeneration has recently been shown to be involved in the initial phases of diabetic retinopathy, raising the possibility of setting up a preventive strategy based on early retinal neuroprotection. To make this possible, it is crucial to identify a biomarker for early retinal neurodegeneration. To this end, in this study, we verified and confirmed that, in the Akita mouse model of diabetes, the thinning of the retinal nerve fiber layer/ganglion cell layer (the RNFL/GCL-the layer that contains the retinal ganglion cells) precedes the death of these same cells, suggesting that this dysfunction is a possible biomarker of retinal neurodegeneration. We then confirmed the validity of this assumption by starting a neuroprotective treatment (based on nerve growth factor eye drops) in concert with the first demonstration of RNFL/GCL thinning. In this way, it was possible not only to avoid the loss of retinal ganglion cells but also to prevent the subsequent development of the microvascular stage of diabetic retinopathy. In conclusion, in the case of diabetes, the thinning of the RNFL/GCL appears to be both a valid biomarker and a pharmacological target of diabetic retinopathy; it precedes the development of vascular dysfunctions and represents the ideal starting point for prevention.
Insights
Diabetic retinopathy can be prevented by targeting early retinal neurodegeneration. Thinning of the retinal nerve fiber/ganglion cell layer (RNFL/GCL) is a key biomarker and therapeutic target for preventing vision loss.
Area of Science:
- Ophthalmology
- Diabetology
- Neuroscience
Background:
- Diabetic retinopathy (DR) involves retinal neurodegeneration in early stages.
- Early detection and neuroprotection are crucial for preventing DR progression.
- Identifying reliable biomarkers for early neurodegeneration is essential.
Purpose of the Study:
- To identify a biomarker for early retinal neurodegeneration in diabetes.
- To evaluate the potential of neuroprotection as a preventive strategy for DR.
- To determine if RNFL/GCL thinning precedes vascular changes in diabetic retinopathy.
Main Methods:
- Utilized the Akita mouse model of diabetes.
- Monitored the retinal nerve fiber layer/ganglion cell layer (RNFL/GCL) for thinning.
- Initiated neuroprotective treatment (nerve growth factor eye drops) upon detecting RNFL/GCL thinning.
Main Results:
- Confirmed that RNFL/GCL thinning precedes ganglion cell death in diabetic mice.
- Demonstrated that early neuroprotective treatment prevents ganglion cell loss.
- Showed that preventing RNFL/GCL thinning halts the development of DR's microvascular stage.
Conclusions:
- RNFL/GCL thinning is a valid biomarker for early diabetic retinopathy.
- RNFL/GCL thinning serves as an effective pharmacological target for DR prevention.
- Intervention at the RNFL/GCL thinning stage prevents vascular complications and vision loss.


