3.2.3 Emerging experimental analysis of diabetic retinopathy
In most preclinical animal models, fluorescein angiography, optical coherence tomography and electroretinography are widely utilized methods to determine the functional changes of diabetic retinopathy. Additionally, inflammation and oxidative stress markers can be quantified by performing histology, real-time PCR, western blots, ELISA, immunohistochemistry and immunofluorescence using specific antibodies.
More recently, the discovery of a novel laser speckle flowgraphy imaging technique has emerged as a rapid and non-invasive method to determine basal blood flow and neuronal activity-dependent alterations in ocular diseases. Not only serving as a useful biomarker to detect and monitor postoperative outcomes for retinal diseases, this technique enables the detection of reduced blood flow volume and dysregulated retinal microvasculature that can cause hypoxia and eventually retinal neovascularization[128]. Moreover, the use of positron emission tomography (PET) imaging using [18F]FP-(+)-DTBZ has been reported as an early diagnostic tool to evaluate diabetic retinopathy in rat models. The [18F]FP-(+)-DTBZ PET targeting of vesicular monoamine transporter 2 (VMAT2) changes have been shown to detect dopaminergic neuron loss in the retina, a known characteristic symptom of early diabetic retinopathy[129].
A major limitation of current screening processes to detect diabetic retinopathy is that disease progression can go undetected until irreversible damage and blindness has occurred. The development of a biomarker for clinical screening would be a useful tool to overcome limitations such as the need for diagnosis by a qualified specialist, which can be costly, thereby restricting the population that can be effectively screened. To overcome this, Tawfik et al evaluated homocysteine (Hcy), a sulfur-containing amino acid known to induce the death of retinal ganglion cells, as a biomarker of diabetic retinopathy[130]. Indeed, an increase in Hcy levels was observed in the serum, vitreous humour and retina of both experimental animal models of diabetes and diabetic patients, while optical coherence tomography and fluorescein angiography has confirmed that Hcy-induced retinal changes in diabetic mice are aggravated[130]. In summary, Hcy should be investigated further as a strong biomarker candidate for diabetic retinopathy screening.
Diabetic neuropathy