The primate fovea: Structure, function and development.

Objective Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO 2 ) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO 2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. Design Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO 2 nanoparticles. The proinflammatory effects of TiO 2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO 2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. Results Oral administration of TiO 2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO 2 -administered mice. In vitro, TiO 2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO 2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. Conclusion These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO 2 nanoparticles.

https://gut.bmj.com/content/gutjnl/66/7/1216.full.pdf

Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome

Purpose The shape of the human fovea presents important but still poorly characterized variations. In this study, the variability of the shape and structure of normal foveae were examined. Methods In a group of 110 eyes of 57 healthy adults, the shape and structure of the fovea were analyzed by automated segmentation of retinal layer on high-resolution optical coherence tomography scans. In an additional group of 10 normal eyes of 10 patients undergoing fluorescein angiography, the size of the foveal avascular zone (FAZ) was correlated to foveal shape. Results From the thickest to the thinnest fovea, there was a structural continuum ranging from a shallow pit with continuity of the inner nuclear layer (INL) over the center (seven eyes; 6.7%), to a complete separation of inner layers overlying a flat and thinner central outer nuclear layer (ONL; eight eyes; 7.3%). Central foveal thickness correlated inversely to the degree of inner layer separation and to the surface of the FAZ. Conclusions Foveal structure strongly correlates with its neurovascular organization. The findings support a developmental model in which the size of the FAZ determines the extent of centrifugal migration of inner retinal layers, which counteracts in some way the centripetal packing of cone photoreceptors.

Foveal shape and structure in a normal population.

Adaptation of the central retina for high acuity vision: cones, the fovea and the avascular zone.

PAX6 missense mutation in isolated foveal hypoplasia

Fifteen patients presented with foveal hypoplasia as an isolated ocular finding. The characteristic findings associated with this entity are a visual acuity of 6/21 or worse, nystagmus, and a typical ophthalmoscopic appearance of the macular area, including absent or abnormal maculofoveal reflexes, unclear definition of the maculofoveal area, and capillaries running abnormally close to the presumed macular area, some of them even crossing the horizontal meridian. Fluorescein angiography revealed a variable and incomplete filtering effect of the choroidal fluorescence in the macular area, suggesting abnormalities in the amount and distribution of macular pigments. The fundal findings of isolated foveal hypoplasia, although typical, are very subtle and often difficult to detect, especially because of the accompanying nystagmus. For this reason we suspect that foveal hypoplasia may be more common than is generally believed.

https://bjo.bmj.com/content/bjophthalmol/71/12/926.full.pdf

Isolated foveal hypoplasia.

Aim To describe the histological changes in the optic nerve (ON) after experimental segregation of cerebrospinal fluid (CSF). Methods In seven sheep, a silicone band was placed around one ON to compress the subarachnoid space (SAS) surrounding the nerve, thus blocking the flow of CSF without compressing the ON itself. After 4 or 21 days, both the ligated and untouched ONs were removed and evaluated histologically. Results All treated ONs showed marked loss of axons, destruction of myelin and swelling of meningoepithelial cells, most pronounced in the proximal ON adjacent to the globe at the location most distant to the ligature. There was no significant difference in histological findings between the ONs that were ligated for 4 days and those with 21 days of ligature. Conclusion CSF segregation in the ON by blocking the SAS leads within 4 days to severe nerve damage. The increasing severity of these changes with increasing distance from the site of the ligature argues against simple pressure- or microperfusion-dependent effects and supports the hypothesis that interruption of CSF flow in the SAS of the ON can produce damage due to a change of CSF flow and content.

https://bjo.bmj.com/content/bjophthalmol/early/2010/05/27/bjo.2009.171660.full.pdf

Shlomo A Dotan

Papers

Isolated foveal hypoplasia.

Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis.