Neurodegenerative Disorders of the Eye and of the Brain: A Perspective on Their Fluid-Dynamical Connections and the Potential of Mechanism-Driven Modeling

Abstract

Neurodegenerative disorders (NDD) such as Alzheimer's and Parkinson's diseases are significant causes of morbidity and mortality worldwide. The pathophysiology of NDD is still debated, and there is an urgent need to understand the mechanisms behind the onset and progression of these heterogenous diseases. The eye represents a unique window to the brain that can be easily assessed via non-invasive ocular imaging. As such, ocular measurements have been recently considered as potential sources of biomarkers for the early detection and management of NDD. However, the current use of ocular biomarkers in the clinical management of NDD patients is particularly challenging. Specifically, many ocular biomarkers are influenced by local and systemic factors that exhibit significant variation among individuals. In addition, there is a lack of methodology available for interpreting the outcomes of ocular examinations in NDD. Recently, mathematical modeling has emerged as an important tool capable of shedding light on the pathophysiology of multifactorial diseases and enhancing analysis and interpretation of clinical results. In this article, we review and discuss the clinical evidence of the relationship between NDD in the brain and in the eye and explore the potential use of mathematical modeling to facilitate NDD diagnosis and management based upon ocular biomarkers.

Mimicking chronic glaucoma over 6 months with a single intracameral injection of dexamethasone/fibronectin-loaded PLGA microspheres

“…Obtaining models of neurodegenerative diseases of the retina is a challenge in the field of ophthalmology (Guidoboni et al., 2020 ). In the case of glaucoma, there are several animal models, among them, rodent animal models that are more convenient.…”

Uncertainty propagation and sensitivity analysis: results from the Ocular Mathematical Virtual Simulator

“…Thanks to its special connection to the brain and its accessibility to measurements, the eye provides a unique window on the brain, thereby offering non-invasive access to a large set of potential biomarkers that might help in the early diagnosis and clinical care of Neuro-Degenerative Diseases [17]. The OMVS has already shown great potentiality to reproduce the ocular biomechanics and the hemodynamics [42].…”

Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

“…Retinal ganglion cell damage is a characteristic of both glaucoma and AD, along with discovery of amyloid-beta and tau protein deposition, For some time, science has been studying if retinal neurodegeneration is predictive for Alzheimer disease (AD) and Parkinson disease (PD). In patients with AD or PD, several studies have shown changes in the nerve fibers of the retina [2]. It was noted that subjects with preclinical AD showed retinal microvascular and structural alterations.…”

“…We see from the eyes, and the information collected reaches specific neurons of visual cortex in the forebrain. The eye provides a unique window of the brain due to its special connection; the retina, photosensitive nerve tissue that covers the inner surface of the eye, is properly considered part of the brain [ 1 , 2 , 3 ]. The typical retina of a mammal contains several different types of neurons ( Figure 1 ), each of which has its own morphology and specific function: The signals of the photoreceptors (rods and cones) are processed in cascade by groups of amacrine, bipolar, and horizontal cells that are in connection with the ganglion cells, responsible for transmitting information to the brain [ 4 ].…”