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