OPTM4102 Blood Ocular Barriers PDF

OPTM4102 Blood ocular barriers Dr. Jason Charng [email protected] Acknowledgement of country The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritu...

OPTM4102 Blood ocular barriers Dr. Jason Charng [email protected] Acknowledgement of country The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge. Artist: Dr Richard Barry Walley OAM Objectives Overview on inflammation and its effects inside the eye ‘Ocular immune privilege’ Sites of blood-ocular barrier, structures involved and changes in inflammation Haemodynamic - review Marieb & Hoehn, Human Anatomy and Physiology, 7th ed Haemodynamic - review https://open.oregonstate.education/ Inflammation ERR Body’s immune system response to an irritant Acute or chronic Involves cells, proteins and other mediators, from both innate and adaptive immune system Initiated by signals from injured cells, or from cells of immune system E Causes ‘controlled’ destabilisation of blood vessels and associated exudation of blood contents And altered blood flow in local area Inflammation Purpose of inflammation Protection response - eliminates cause of injury (if any residual) - limits geographic extent of consequences of injury - prevents sequelae of injury (e.g. secondary infection) Initiates the healing and regeneration process Inflammation is a good thing But if inflammation too aggressive can do more damage than injury (anti-inflammatory drugs) Clinical signs of inflammation Signs of acute inflammation ~ Rubor - redness ~ Calor - heat ~ Tumor - swelling ~ Dolor - pain Lead to loss of function  Cells of inflammation innate immune Part of Cells , involved in the removal of tumour O cells - part of the adaptive O - immune response do B-lymphocytesthe not generate activated but the antibodies Cells form called plasia antibodies. generate ↳ innate immune cell , present antigens to the adaptive immune cell Inflammation in the eye Eye with red conjunctiva Ocular surface allergy (e.g. seasonal allergic conjunctivitis) eosinophil cells and serous fluid Corneal infection (e.g. bacterial keratitis) neutrophil cells – both inside AC and in corneal tissue; and spills off ocular (Yanoff and Fine, 2002) surface Inflammation in the eye light bouncing from thekes Alightingone. Anterior chamber reaction (e.g. anterior uveitis) cells ↑ (various depending on cause) and proteins (fibrin) In healthy eye, the anterior chamber ↓ should be clear , Anterior chamber Chorioretinal inflammation (e.g. posterior uveitis in toxoplasma infection) cells and proteins  Ocular immune privilege Cell and protein response in inflammation inside eye can reduce vision (both short term and lead to permanent visual loss) *** 1/l AFTER T EnhTat #13 System exists to ensure that excessive immune response inside eye is limited – ‘ocular immune privilege’ PERFEHE, TH. supression of the immune system ↓ Evidence for ocular immune privilege: E transplant rejection. ~ Success of corneal transplantation by far the most successful organ transplantation m ~ Unrestricted growth of non-self tumour cells inside the eye the immune system didn't => recognise the tumour cells ~ Aqueous and vitreous fluids inhibit inflammatory cells in vitro in the eye. - > there factors inside the eye that supprese the immune are response. Ocular immune privilege Signalling protein TGF-β2 high ! levels in eye - not so in most other body tissues Produced by RPE, and pigment epithelium of ciliary body and iris This signalling protein ‘disarms’ (Yoshida et al, 2000) inflammatory cells that cross from blood stream into eye  Blood ocular barriers 3 Main sites of barriers: Q Iris (blood-aqueous barrier) ② Ciliary body (blood-aqueous barrier) ③ Retina (blood-retina barrier; 2 separate locations) Blood ocular barrier - iris Dye stay within iris blood vessels Minimal dye detected in aqueous => demonstrated that there is a barrier to prevent things Passage of macromolecules - minimised Blood ocular barrier - iris Light microscopy: Dye marker clearly retained in lumen of blood vessels Capillaries not fenestrated Important as no epithelial barrier on the anterior surface of the iris - blood products would otherwise leak into the aqueous and decrease vision Blood ocular barrier - iris Electron microscopy: vessel endothelial cells “stitched” together Tight junctions (and related junctions) form the cell-cell bond Endothelial cells interwoven to increase surface area of binding - aids strength Tight junctions between vascular endothelium: blood-aqueous barrier in iris Blood ocular barrier – ciliary body Light microscopy: Dye marker leaks from blood vessels into ciliary body tissue Unlike iris, blood vessels in ciliary stroma leak Ciliary blood vessels provide no barrier to macromolecules - No leakage outside the ciliary stroma – barrier within the epithelial cells Blood ocular barrier – ciliary body Blood ocular barrier – ciliary body (Raviola et al, 1977) Blood-aqueous barrier breakdown Inflammatory cells and proteins mix with aqueous when iris and ciliary body inflamed Tight junctions break down in inflammation allowing this to happen Proteins usually mainly fibrin Cells depend on what is causing the inflammation – usually lymphocytes and macrophages, or neutrophils Blood ocular barrier – retina Blood ocular barrier – retina Light microscopy: Retinal vessels do not leak marker dye (implies tight junctions in capillaries, as in iris) Choroidal vessels freely - leak marker dye, but not - into retina (implies -- fenestrated blood vessels - and tight junctions - between RPE, as in ciliary - body) - Blood ocular barrier – retina Electron microscopy: Marker dye moves into choroidal tissue through fenestrations in choriocapillaris Inner retinal vessels tight junctions in capillary endothelium - non- fenestrated Blood ocular barrier – retina Choriocapillaris fenestrations ‘polarised’ to retina-facing membrane Suggests designed to target delivery of blood products to retina Blood ocular barrier – retina (Fronk and Vargis, 2016) Blood ocular barrier – RPE as filter https://pubmed.ncbi.nlm.nih.gov/15987797/  5 methods material can pass through RPE. Blood ocular barrier – RPE as filter Retina Choroid requires energy (Xia and Rizzolo, 2017) Summary Process and purpose of inflammation, cells involved Ocular immune privilege Main sites of blood ocular barrier Inflammation causes breakdown of tight junctions and therefore cellular barriers Blocker Barrier Blood Aqueoy Barrier (BAB) Blood - Retinal Barrier (BRB) > - Separates the blood from the aquery > - Separate blood from the neural retina. humor in the anterior chamber of (divide into 2 parts). the - non-fenestrated eye. - non-fenestrated ① Inner BRB Non pigmented Ciliary epithelial cells · - btw > - line the ciliaty body > - formed by the right junctions > - regulate the secretion of aqueous humor retinal capillary endothelial cells. I. - allow the passage of moluculars · > - Prevents large molecules & cells Endothelial cells of the Tris vasculature. from the retina > - Have tight junction that restrict entering - passage of The substances. & Outer BRB > - formed by the retinal pigment epithelium (RPE) cells > - controls the exchange of substances btw the choroid & the retina.