Understanding how ageing impacts ganglion cell susceptibility to injury in glaucoma.

Glaucoma is a leading cause of blindness worldwide, with a marked increase in prevalence with advancing age. Due to the multifactorial nature of glaucoma pathogenesis, dissecting how ageing impacts upon glaucoma risk requires analysis and synthesis of evidence from a vast literature. While there is a wealth of human clinical studies examining glaucoma pathogenesis and why older patients have increased risk, many aspects of the disease such as adaptations of retinal ganglion cells to stress, autophagy and the role of glial cells in glaucoma, require the use of animal models to study the complex cellular processes and interactions. Additionally, the accelerated nature of ageing in rodents facilitates the longitudinal study of changes that would not be feasible in human clinical studies. This review article examines evidence derived predominantly from rodent models on how the ageing process impacts upon various aspects of glaucoma pathology from the retinal ganglion cells themselves, to supporting cells and tissues such as glial cells, connective tissue and vasculature, in addition to oxidative stress and autophagy. An improved understanding of how ageing modifies these factors may lead to the development of different therapeutic strategies that target specific risk factors or processes involved in glaucoma.

Age-related deficits in retinal autophagy following intraocular pressure elevation in autophagy reporter mouse model.

This study quantified age-related changes to retinal autophagy using the CAG-RFP-EGFP-LC3 autophagy reporter mice and considered how aging impacts autophagic responses to acute intraocular pressure (IOP) stress. IOP was elevated to 50 mm Hg for 30 minutes in 3-month-old and 12-month-old CAG-RFP-EGFP-LC3 (n = 7 per age group) and Thy1-YFPh transgenic mice (n = 3 per age group). Compared with younger eyes, older eyes showed diminished basal autophagy in the outer retina, while the inner retina was unaffected. Autophagic flux (red:yellow puncta ratio) was elevated in the inner plexiform layer. Three days following IOP elevation, older eyes showed poorer functional recovery, most notably in ganglion cell responses compared to younger eyes (12 months old: -33.4 ±â€¯5.3% vs. 3 months mice: -13.4 ±â€¯4.5%). This paralleled a reduced capacity to upregulate autophagic puncta volume in the inner retina in older eyes, a response that was seen in younger eyes. Age-related decline in basal and stress-induced autophagy in the retina is associated with greater retinal ganglion cells' susceptibility to IOP elevation.

Measuring the Full-Field Electroretinogram in Rodents.

Electroretinography allows for noninvasive functional assessment of the retina and is a mainstay for preclinical studies of retinal function in health and disease. The full-field electroretinogram is useful for a variety of applications as it returns a functional readout from each of the major cell classes within the retina: photoreceptors, bipolar cells, amacrine cells, and retinal ganglion cells. Rodent models are commonly employed in ocular degeneration studies due to the fast throughput of these mammalian species and the conservation of the electroretinogram from the preclinic to the clinic. Here we describe approaches for in vivo electroretinography in rodent models.

Retinal Assessment Using In Vivo Electroretinography and Optical Coherence Tomography in Rodent Models of Diabetes.

Electroretinography and optical coherence tomography imaging allow for non-invasive quantitative assessment of the retina. These approaches have become mainstays for identifying the very earliest impact of hyperglycemia on retinal function and structure in animal models of diabetic eye disease. Moreover, they are essential for assessing the safety and efficacy of novel treatment approaches for diabetic retinopathy. Here, we describe approaches for in vivo electroretinography and optical coherence tomography imaging in rodent models of diabetes.