The Chemistry of the Eye/Body in Glaucoma

Chat Highlights
February 16, 2005

Norma Devine, Editor

On Wednesday, February 16, 2005, Dr. Rick Wilson, a glaucoma specialist at Wills, and the glaucoma chat group discussed "The Chemistry of the Eye/Body in Glaucoma."

Moderator:  Tonight's topic concerns the chemistry of the eye and glaucoma.  (Chemistry is defined as a science that deals with the composition, structure, and properties of substances and with the transformations they undergo.)

Dr. Rick Wilson:  That is a deep subject, so I am not sure people want to hear me ramble on about how aqueous is made, etc.  Perhaps we could see if anyone has specific questions.

P:  I am a little confused about the topic.  Does it concern the chemical makeup of the eye or also the function of the parts of the eye or the lack thereof?

Dr. Rick Wilson:  Anything you want to ask that I can answer.

P:  Can you tell us how eyedrops affect the chemistry of the eye and body?

Dr. Rick Wilson:  Which eyedrops?

Moderator:  Let’s start with prostaglandins, such as Xalatan.

Dr. Rick Wilson:  Prostaglandins increase outflow of aqueous from the eye by uveoscleral outflow -- the flow of aqueous posteriorly from the anterior chamber between the muscle bundles of the muscle that focuses the lens in the eye.  The IOP (intraocular pressure) drops significantly by markedly increasing the outflow.

Moderator:  So, is there a chemical effect that makes the muscles contract more, or rhythmically?

Dr. Rick Wilson:  No, prostaglandins dissolve the cement substance between the muscle bundles, which allows fluid to flow much more easily through them posteriorly.  The fluid makes its way out through the white scleral coat of the eye.

Dr. Rick Wilson:  Carbonic anhydrase inhibitors (CAI) block carbonic anhydrase II, an enzyme that is part of the aqueous production.  Blocking that enzyme blocks some of the aqueous production.

P:  Don't naturally occurring prostaglandins promote the growth of existing tumors?  Are there any other theoretical downsides to a chronic state of artificially induced inflammation with prostaglandin analogs?

Dr. Rick Wilson:  Prostaglandins are akin to the chemical that causes tanning in your skin in response to the sun.  Therefore, they can cause darkening of the iris in some individuals and increased pigmentation of the skin around the eye.  They also cause eyelashes to grow abnormally long and dark.

P:  With prostaglandin analogs, does the restructuring of the ciliary body's extracellular matrix affect the supposed pressure insensitivity of the uveoscleral route?  That is, do prostaglandins make the uveoscleral route more responsive to elevations in IOP similar to trabecular outflow?

Dr. Rick Wilson:  Prostaglandins increase gross aqueous flow, but the response is a much flatter curve vis-à-vis IOP (intraocular pressure) than is the outflow through the trabecular meshwork.  As you mention, the higher the IOP, the faster the flow out through the trabecular meshwork until the IOP gets high enough to collapse Schlemm's canal, at which point outflow drops dramatically.

P:  Does a prostaglandin have a permanent effect on the eye, not just on the color but on what it does to the cells?

Dr. Rick Wilson:  The changes produced in the ciliary body muscle take at least six weeks to revert to normal.  The only permanent change we know of is the change in the color of the eye.

P:  Why is it recommended that prostaglandins be taken at night?

Dr. Rick Wilson:  Because they dilate the vessels on the surface of the eye, and it is cosmetically more acceptable to have a red eye while you sleep rather than all morning.

Moderator:  I'm sure people would like a short version of the chemistry of aqueous production.

Dr. Rick Wilson:  Aqueous humor formation occurs along crests of the ciliary processes by three mechanisms:

(1) Ultrafiltration: Passive flow of water and water soluble substances through theoretical micropores by osmotic gradient or hydrostatic pressure

(2) Diffusion: Passive movement of ions across a membrane related to charge and concentration

(3) Active transport (secretion): Active transport of larger water- soluble substances, or those with a greater charge, across cell membranes against an electrochemical gradient

Ultrafiltration is the pressure-dependent component influenced by IOP, blood pressure in the ciliary capillaries, and plasma oncotic pressure.  [The term oncosis (derived from onkos, meaning swelling) means cell death with swelling.]  That is, if the IOP is 15 mm Hg, and the oncotic pressure is toward stroma 12, more than 27 mm Hg capillary pressure is needed to get bulk flow.

Active transport of Na+, Ca++, HCO3-, ascorbic acid, and amino acids causes the osmotic gradient, which leads to ultrafiltration and diffusion with increased levels of H+, Cl-, and ascorbic acid and decreased bicarbonate and minimal protein levels in posterior chamber aqueous compared to plasma.

P:  What is the aqueous made up of?  What about making aqueous thicker or thinner depending on the what the person needs to improve or decrease flow?

Dr. Rick Wilson:  Trabecular meshwork outflow equals conventional outflow.  There is unimpeded flow through the trabecular meshwork and juxtacanalicular apparatus until the endothelial lining of Schlemm's canal is reached.  Aqueous passes passively through this endothelium, both across the cell through giant vacuoles and between cells.  Epinephrine and isoproterenol increase flow across the endothelial cells lining Schlemm’s canal and trabecular meshwork by a beta-receptor mediated response that reduces cell area and widens intercellular space. That reduces resistance to aqueous passage.

Dr. Rick Wilson:  If the eye is inflamed, protein is passed into the eye from the inflamed blood vessels and increases the viscosity of the aqueous.  That decreases the ease with which aqueous leaves the eye and the IOP can rise.  Inflammation can also liberate natural prostaglandins, which can lower the IOP. It's even more complex, but probably inappropriate for this chat room.

Moderator:  Thanks for providing that explanation.

P:  Why are all babies (and kittens) born with blue eyes?

Dr. Rick Wilson:  I assume, but have no definite knowledge, that it is because it takes longer in development to elaborate the pigment (melanin).  That is, blue is the absence of pigment, and it takes time to make enough pigment to darken the eyes. Peoples' eyes often darken throughout childhood.

End of highlights for February 16, 2005.

On Febuary 23, Dr. Henderer discussed "Neuroprotection Update" in the Chat room. Click here for highlights of that meeting.

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