Variability in Retinal Neuron Populations and Associated Variations in Mass Transport Systems of the Retina in Health and Aging

Zouache, Moussa A.

doi:10.3389/fnagi.2022.778404

Cited by 11 publications

(21 citation statements)

References 306 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These include the physical characteristics of the choriocapillaris/outer retina interface, and solute concentrations in retinal tissue (Zouache et al., 2019). The choriocapillaris has evolved several features that facilitate transfers across endothelial cells, including fenestrations (Zouache, 2022). Refined models are necessary to determine the differential contribution of these structures to mass transfers to the outer retina, including in the vicinity of diffusion‐limited regions.…”

Section: Discussionmentioning

confidence: 99%

“…The salient features of mass transfers between choriocapillaris and outer retina may be inferred from oxygen concentration profiles extracted invasively from animal eyes (Linsenmeier & Zhang, 2017). Measures of veno–arterial difference in the concentration of glucose and oxygen obtained from the choroid of cats and pigs have been used to estimate bulk transfers between choriocapillaris and outer retina (Wang, Kondo et al., 1997; Wang, Törnquist et al., 1997; Zouache, 2022; Zouache et al., 2016). These methods are, however, not adapted to detect spatial variabilities in transfers at the scale of a group of functional lobules.…”

Section: Discussionmentioning

confidence: 99%

“…Despite its key role in vision, our understanding of the choriocapillaris and its importance in maintaining photoreceptor homeostasis is limited. This is mainly due to its unusual anatomy, which has proven difficult to reconcile with in vivo visualisations of the blood flow within its plane and with frameworks describing mass exchange with the outer retina (Zouache, 2022). This lack of understanding has hindered our ability to determine the contribution of choriocapillaris impairments to the visual dysfunction associated with ageing and inflammatory and degenerative diseases of the back of the eye.…”

Section: Introductionmentioning

confidence: 99%

“…This lack of understanding has hindered our ability to determine the contribution of choriocapillaris impairments to the visual dysfunction associated with ageing and inflammatory and degenerative diseases of the back of the eye. Increasing age is associated with a general loss of choriocapillaris vessels and a possible reduction of its thickness (Zouache, 2022). In age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide (Health Organisation, 2014;Wong et al, 2014), both structural (Mullins et al, 2011;Seddon et al, 2016;Spraul et al, 1996Spraul et al, , 1999 and functional (Ciulla et al, 1999;Pauleikhoff et al, 1999;Mendrinos & Pournaras, 2009) changes have been reported.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina

Faust,

Klettner,

Toso

et al. 2024

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Vision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non‐random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion‐limited regions represent areas of reduced exchange with the outer retina. The width of diffusion‐limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina. imageKey points The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina. The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body. Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina. Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina

Faust,

Klettner,

Toso

et al. 2024

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The distribution of photoreceptors in the retina is heterogeneous, with a higher concentration in the parafovea, for rods, and fovea, for cones [306]. While appropriate blood supply is necessary to maintain vision, retinal blood vessels can interfere with light and hinder vision.…”

Section: Blood Supply To the Retinamentioning

confidence: 99%

Advancing treatment of retinal disease through in silico trials

2023

View full text Add to dashboard Cite

Treating retinal diseases to prevent sight loss is an increasingly important challenge. Thanks to the configuration of the eye, the retina can be examined relatively easily in situ. Owing to recent technological development in scanning devices, much progress has been made in understanding the structure of the retina and characterising retinal biomarkers. However, treatment options remain limited and are often of low efficiency and efficacy.In recent years, the concept of in silico clinical trials has been adopted by many pharmaceutical companies to optimise and accelerate the development of therapeutics. In silico clinical trials rely on the use of mathematical models based on the physical and biochemical mechanisms underpinning a biological system. With appropriate simplifications and assumptions, one can generate computer simulations of various treatment regimens, new therapeutic molecules, delivery strategies and so forth, rapidly and at a fraction of the cost required for the equivalent experiments. Such simulations have the potential not only to hasten the development of therapies and strategies but also tooptimise the use of existing therapeutics.In this paper, we review the state-of-the-art in in silico models of the retina for mathematicians, biomedical scientists and clinicians, highlighting the challenges to developing in silico clinical trials. Throughout this paper, we highlight key findings from in silico models about the physiology of the retina in health and disease. We describe the main building blocks of in silico clinical trials and identify challenges to developing in silico clinical trials of retinal diseases.

show abstract