10/12/2018 Glaucoma Ted W. Reid, Ph.D. Ciliary Body The trabecular Meshwork • Produces fluid that is pumped into the eye • This fluid is important in maintaining the pressure of the eye. • The pressure of a normal eye is 16mm Hg. 1 10/12/2018 Corneal Limbus Site of Epithelial Stem Cells The Limbus - Trabecular Meshwork Aqueous outflow Trabecular Meshwork Outflow channels for aqueous humor The Retina Schlemms Canal Note the extensive vasculature of the retina. The retina has 5 times the oxygen Content of any other tissue in the body 2 10/12/2018 What is glaucoma ERG Effect of 30 minutes of glucose free medium for the superfused rat retina What is glaucoma What is glaucoma • A disease of the eye which causes a gradual • A disease of the eye which causes a gradual degeneration of retinal ganglion cells (cells degeneration of retinal ganglion cells (cells going to the brain) going to the brain) • A disease where the primary risk factor is an increase in pressure of the eye What is glaucoma What is glaucoma • A disease of the eye which causes a gradual • A disease of the eye which causes a gradual degeneration of retinal ganglion cells (cells degeneration of retinal ganglion cells (cells going to the brain) going to the brain) • • A disease where the primary risk factor is an A disease where the primary risk factor is an increase in pressure of the eye increase in pressure of the eye • A disease that is treated with drugs that lower • A disease that is treated with drugs that lower eye pressure eye pressure • A disease that is treated with surgery to lower eye pressure 3 10/12/2018 What is glaucoma How does Glaucoma cause blindness • A disease of the eye which causes a gradual • Current thinking is that the pressure causes degeneration of retinal ganglion cells (cells going to the brain) glaucoma • A disease where the primary risk factor is an increase in pressure of the eye • A disease that is treated with drugs that lower eye pressure • A disease that is treated with surgery to lower eye pressure • A disease that is one of the leading causes of blindness How does Glaucoma cause blindness How does Glaucoma cause blindness • Current thinking is that the pressure causes • Current thinking is that the pressure causes glaucoma glaucoma • How does the pressure cause glaucoma? • How does the pressure cause glaucoma • It restricts the blood flow to the retina How does Glaucoma cause blindness Note the extensive vasculature of the retina. • Current thinking is that the pressure causes The retina has 5 times the oxygen Content of any other tissue in the body glaucoma • How does the pressure cause glaucoma • It restricts the blood flow to the retina • Is this the whole story? 4 10/12/2018 Old Results High IOP a Stress Factor • Some people with no increase in pressure • Stress is known to trigger autoimmune experience the same destruction to their responses. retina. • Progressive loss of nerve cells can continue in patients whose IOP is controlled. High IOP a Stress Factor High IOP a Stress Factor • Stress is known to trigger autoimmune • Stress is known to trigger autoimmune responses. responses. • What is autoimmune –it is when our • What is autoimmune –it is when our antibodies start to react with our own body. antibodies start to react with our own body. • In patients with glaucoma they find antibodies against their own heat shock proteins What is a heat shock protein? What is a heat shock protein? • It is a family of proteins in our body. • It is a family of proteins in our body. • They are made in cells under different kinds of stress (heat, cold, UV light and wound healing). 5 10/12/2018 What is a heat shock protein? What is a heat shock protein? • It is a family of proteins in our body. • It is a family of proteins in our body. • They are made in cells under different kinds of • They are made in cells under different kinds of stress (heat, cold, UV light and wound stress (heat, cold, UV light and wound healing). healing). • They help to heal proteins damaged by stress. • They help to heal proteins damaged by stress. • They are found in all species –even bacteria. Authors Hypothesis Authors Hypothesis • High pressure somehow produces antibodies • High pressure somehow produces antibodies to heat shock proteins (HSP) to heat shock proteins (HSP) • Human glaucoma patients are found to have antibodies to their HSP Authors Hypothesis Authors Hypothesis • High pressure somehow produces antibodies • High pressure somehow produces antibodies to heat shock proteins (HSP) to heat shock proteins (HSP) • Human glaucoma patients are found to have • Human glaucoma patients are found to have antibodies to their HSP antibodies to their HSP • These antibodies are also against HSP from • These antibodies are also against HSP from bacteria. bacteria. • These antibodies start to attack the patient’s own HSP 6 10/12/2018 Where do these antibodies come from Where do these antibodies come from • HSP from bacteria are very similar to our HSP • HSP from bacteria are very similar to our HSP • The antibodies may have been produced in the past against bacteria in our body. Where do these antibodies come from Where do these antibodies come from • HSP from bacteria are very similar to our HSP • HSP from bacteria are very similar to our HSP • The antibodies may have been produced in • The antibodies may have been produced in the past against bacteria in our body. the past against bacteria in our body. • IOP stress produces HSP in our eye. • IOP stress produces HSP in our eye. • The IOP also damages the blood retinal barrier Where do these antibodies come from Where do these antibodies come from • HSP from bacteria are very similar to our HSP • HSP from bacteria are very similar to our HSP • The antibodies may have been produced in • The antibodies may have been produced in the past against bacteria in our body. the past against bacteria in our body. • IOP stress produces HSP in our eye. • IOP stress produces HSP in our eye. • The IOP also damages the blood retinal barrier • The IOP also damages the blood retinal barrier • This allows the antibodies to the bacteria to • This allows the antibodies to the bacteria to get into the eye. get into the eye. • The antibodies interact with T‐cells 7 10/12/2018 The authors also showed: The authors also showed: • High IOP allowed T‐cells to penetrate the • High IOP allowed T‐cells to penetrate the blood‐retinal barrier blood‐retinal barrier • Inducing high IOP in mice with no T‐cells showed little damage and no progression of disease after pressure was returned to normal. Take Home Message Take Home Message • Probably the role of the increased pressure in • New treatments should be focused on this the eye is to cause damage to the tight immune response. junctions of the retina. • Damage allows the immune molecules to enter the retina. • These immune molecules can attach molecules in the retina that are similar to those found on bacteria. • This causes a slow destruction of the retina. 8.