Glaucoma Ciliary Body

Home , Ciliary body, Trabecular meshwork

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.

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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

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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 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

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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?

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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).

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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 • 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

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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 • 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

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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.