Ocular Health of Octodon degus as a Clinical Marker for Age-Related and Age-Independent Neurodegeneration.

The aging process and age-related diseases such as Alzheimer's disease (AD), are very heterogeneous and multifactorial, making it challenging to diagnose the disease based solely on genetic, behavioral tests, or clinical history. It is yet to be explained what ophthalmological tests relate specifically to aging and AD. To this end, we have selected the common degu (Octodon degus) as a model for aging which develops AD-like signs to conduct ophthalmological screening methods that could be clinical markers of aging and AD. We investigated ocular health using ophthalmoscopy, fundus photography, intraocular pressure (IOP), and pupillary light reflex (PLR). The results showed significant presence of cataracts in adult degus and IOP was also found to increase significantly with advancing age. Age had a significant effect on the maximum pupil constriction but other pupil parameters changed in an age-independent manner (PIPR retention index, resting pupil size, constriction velocity, redilation plateau). We concluded that degus have underlying factors at play that regulate PLR and may be connected to sympathetic, parasympathetic, and melanopsin retinal ganglion cell (ipRGC) deterioration. This study provides the basis for the use of ocular tests as screening methods for the aging process and monitoring of neurodegeneration in non-invasive ways.

Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus.

Accumulation of amyloid-beta (Aß) peptides is regarded as the hallmark of neurodegenerative alterations in the brain of Alzheimer's disease (AD) patients. In the eye, accumulation of Aß peptides has also been suggested to be a trigger of retinal neurodegenerative mechanisms. Some pathological aspects associated with Aß levels in the brain are synaptic dysfunction, neurochemical remodeling and glial activation, but these changes have not been established in the retina of animals with Aß accumulation. We have employed the Octodon degus in which Aß peptides accumulated in the brain and retina as a function of age. This current study investigated microglial morphology, expression of PSD95, synaptophysin, Iba-1 and choline acetyltransferase (ChAT) in the retina of juvenile, young and adult degus using immunolabeling methods. Neurotransmitters glutamate and gamma-aminobutyric acid (GABA) were detected using immunogold labeling and glutamate receptor subunits were quantified using Western blotting. There was an age-related increase in presynaptic and a decrease in post-synaptic retinal proteins in the retinal plexiform layers. Immunolabeling showed changes in microglial morphology characteristic of intermediate stages of activation around the optic nerve head (ONH) and decreasing activation toward the peripheral retina. Neurotransmitter expression pattern changed at juvenile ages but was similar in adults. Collectively, the results suggest that microglial activation, synaptic remodeling and neurotransmitter changes may be consequent to, or parallel to Aß peptide and phosphorylated tau accumulation in the retina.

Prevalence of diabetic retinopathy at first presentation to the retinal screening service in the greater Wellington region of New Zealand 2006-2015, and implications for models of retinal screening.

AIM: To describe the prevalence of diabetic retinopathy (DR) in patients at first presentation for diabetic retinal screening in the greater Wellington region with the intent of service evaluation. METHODS: This is a retrospective study using data collected from patients newly referred for diabetic retinal screening between 2006-2015 (prevalence analysis, n=12667). The prevalence of DR was calculated by gender, ethnicity, age, type of diabetes and glycaemic control (HbA1c). Chi-square test and multiple logistic regression was used for data analysis. RESULTS: The prevalence of any DR was 22.5% (n=2852) (non-sight-threatening (NST-DR) n=2562, 20.2%, sight-threatening (ST-DR) n=290, 2.3%). Type 1 diabetes and poor HbA1c control were strongly associated with any degree of DR. Old-age (>65 years), and Asian and Pacific Island (PI) ethnicity had moderately greater odds compared with European. Male gender had marginally increased odds for any DR. CONCLUSION: This study identified a large proportion (97.7%) of patients (no DR n=9815, 77.5%, NST-DR n=2562, 20.2%) who can be managed in the community by appropriately supported primary care providers, and do not require referral to secondary care ophthalmology. In addition to early detection of ST-DR (2.3%), retinal screening is an early opportunity for education of patients with no DR or NST-DR.

Alzheimer's Disease-Related Protein Expression in the Retina of Octodon degus.

New studies show that the retina also undergoes pathological changes during the development of Alzheimer's disease (AD). While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with Aß aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. Aß4G8 and Aß6E10 detected Aß peptides in some of the young animals but the expression was higher in the adults. Aß peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL) and ganglion cell layer (GCL). Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected Aß oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months) animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that Aß peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye.