scientific basis of vision iris, ciliary body and lens shiva swamynathan department of ophthalmology...
TRANSCRIPT
Scientific Basis of Vision
Iris, Ciliary Body and Lens
Shiva SwamynathanDepartment of Ophthalmology
University of Pittsburgh School of Medicine
Uveal Tract – Vascular middle layer of the eyeIris (Anterior), Ciliary Body (Middle), Choroid (Posterior)
Iris: Pigmented diaphragm located between anterior and posterior chambers. Regulates the amount of light reaching the retina.
Ciliary Body: Regulates the composition and production of aqueous humor, affecting the ionic environment and metabolism of the lens, iris, TM and cornea.
Choroid: Vascular layer of the eye located between the retina and the sclera. Provides nourishment and oxygen to outer layers of the retina.
Where is the uveal tract attached to the sclera?
1.The scleral spur2.The exit points of vortex veins 3.The optic nerve.
Anterior Border- An incomplete layer of endothelial (mesothelial) cells.
The Irideal Stroma accounts for most of the mass of the iris. Composed of connective tissue, blood vessels and nerve fibers. Pigmented cells containing melanin are scattered within the stroma. The posterior boundary of the stroma, peripheral to the sphincter muscle, is demarcated by a sheet of smooth muscle, the dilator muscle.
The pigmented epithelium is composed of two layers of densely pigmented cells.
Anatomy of the Iris
SphincterPigmented epitheliumAnterior BorderStromaDilator
Blood Supply to the Iris
Source: The major arterial circle in the ciliary body. The blood vessels of the iris run in a radial direction. The anterior border layer contains very few vessels.
Innervation of the Iris
The iris is supplied by the ciliary nerves, which pierce the sclera around the optic nerve and run forward in the perichoroidal space.
After reaching the iris the ciliary nerves form a plexus around its attached margin, from which the nerve fibers ending in the anterior surface of the iris, Sphincter and Dilator are derived.
Sphincter muscle. Encircles the pupil, and constricts the pupil in bright light or during accommodation. Controlled by parasympathetic nerve fibers.
Dilator muscle. Arranged radially, these fibers extend from the base of the iris to the sphincter muscle.Controlled by sympathetic nerve fibers, although some parasympathetic fibers are associated with it.
Iridial Muscles- Sphincter and Dilator (derived from neural ectoderm)
Main functions of iris and ciliary body smooth muscle
1. Contraction/relaxation2. Receptor characterization3. Second messenger formation and regulation4. Arachidonic acid release and eicosanoid biosynthesis
Ciliary Body
Pigmented epithelium is leaky while non-pigmented epithelium facing the aqueous is responsible for the blood-aqueous barrier
1. Produces aqueous fluid that fills the anterior chamber, maintaining IOP 2. The ciliary muscle facilitates lens accommodation
What is the rate of aqueous humor production in humans? About 2-3 l/min.
How does aqueous humor enter the posterior chamber? Actively or Passively?
Actively- Energy dependent secretion carbonic anhydrase-II activity dependent.
Passively- Diffusion and Ultrafiltration.
Active secretion accounts for the bulk of aqueous humor
What is the effect of Carbonic Anhydrase-II inhibitors on aqueous flow?
CA-II inhibitors reduce the rate of entry of sodium and bicarbonate into the aqueous, thus reducing the aqueous humor formation.
True/False: Aqueous humor is rich in macromolecules False.Aqueous humor is practically free of macromolecules, allowing for optical clarity. For example, it contains about 1/500 of the albumin present in the plasma.
Aqueous fluid outflow
The aqueous fluid produced by the ciliary body flows between the iris and lens, through the pupil to the drainage angle at the junction of the iris and the cornea, and exits the eye through the trabecular meshwork and Schlemm’s canal, interscleral channels and episcleral vein.
Eicosanoids
Signaling molecules with hormonal activity, made by oxygenation of 20-carbon essential fatty acids. They control inflammation and serve as messengers in the CNS. They include compounds such as prostaglandins, prostacyclins, thromboxanes, and leukotrienes.
Eicosanoids are derived from either omega-3 (ω-3) or ω-6 EFAs. Unlike the ω-3's, ω-6 eicosanoids are generally pro-inflammatory. Anti-inflammatory drugs such as aspirin and other NSAIDs act by downregulating eicosanoid synthesis.
They play critical roles in regulating aqueous production and outflow.
Prostaglandin Synthesis
A.In response to cytokines, neurotransmitters or pharmacologic treatments, phospholipase-A2 is activated, releasing arachidonic acid from membrane phospholipids
B.Free arachidonic acid is converted to prostaglandin H2 endoperoxide intermediates by cyclooxygenase-I (Cox1; ubiquitously expressed) or Cox2 (expressed in pro-inflammatory conditions)
C.Free arachidonic acid can be metabolized through 5’-lipoxygenases and cytochrome P-450 pathways to generate leukotrienes and epoxides, respectively.
D.Phospholipase A2 can be inhibited by corticosteroids; Cox1 by non-steroidal anti-inflammatory drugs (NSAIDS); and the 5-lipoxygenase pathway by nordihydroguaiaretic acid (NDGA).
True or False?
Neurotransmitters and Receptors in the Iris and Ciliary Body
• Sphincter and ciliary muscles contain cholinergic muscarinic type receptors and are innervated by the parasympathetic third cranial oculomotor nerve.
• Dilator muscles contain -adrenergic type receptors and are innervated by sympathetic nerves from the superior cervical ganglion. Adrenergic impulses are transmitted to the muscles by norepinephrine
• Irideal muscles also contain sensory nerves. Sensory neurotransmitters substance P and calcitonin gene-related peptide (cgrp) may regulate inflammatory reactions and irideal muscle tone.
Muscle Receptor AgonistsSphincter Cholinergic Ach, Muscarine (&Ciliary) Nicotine
Dilator Adrenergic Norepinephrine, Phenylephrine…
Miotic agents Cholinergic agonists stimulate the sphincter (Constrict the pupil) and result in increased accommodation.
Adrenergic blockers block the dilator.
Mydriatic agents Adrenergic agonists stimulate the dilator (Dilate the pupil) Cholinergic blockers block the sphincter and
act as cycloplegics by blocking ciliary muscles.
Muscle Receptor AgonistsSphincter Cholinergic Ach, Muscarine (&Ciliary) Nicotine
Dilator Adrenergic Norepinephrine, Phenylephrine…
Effect of miotic and mydriatic agents on iris and ciliary muscles
Mode of action of anti-glaucoma agents
Primary Mechanism of Action
Drug Class Examples
1. Decreases aqueous humor production
a. -adrenergic antagonists
b. 2-adrenergic agonists
a. Timolol, Betaxolol, Carteolol, Levobunololb. Apraclonidine, Brimonidine
2. Increases trabecular outflow
a. Mioticsb. Adrenergic Agonists
a. Pilocarpineb. Epinephrine, Dipivalyl epinephrine
3. Increases uveoscleral outflow
a. Prostaglandinsb. -Adrenergic Agonists
a. Latanoprost, Bimatoprost, Travoprostb. Apraclonidine, Brimonidine
The choroid • Posterior segment of the uveal tract, located between retina and sclera• Provides nutrients and oxygen to the outer layers of the retina• Blood from the choroidal vessels drains via the four vortex veins • Choroid is bounded by Bruch's membrane and the sclera
Bruch’s MembraneRetinal Pigment Epithelium
Choriocapillaris
Suprachoroidal space
Sclera
Medium Choroidal Vessels
Large Choroidal Vessels
Lens•Lens consists of an external capsule, anterior single cell layered epithelium, equatorial differentiating zone, and the fiber cells in the rest of the tissue. •Lens fiber cells are protein-filled sacks lacking nucleus and organelles.•Lens nucleus consists of the central fiber cells produced from embryonic through adolescence stage (among the oldest cells in the body). •Lens cortex consists of the outer fibers laid down after adolescence. New fiber cells are added to the lens margin throughout life.
Lens Fiber Cell Membranes
• Tightly packed with fairly low fluidity• High amount of saturated fatty acids • High cholesterol:phospholipid ratio, and a • High concentration of sphingomyelin • Lipids contribute about 1% of total lens mass
Name the major lens-specific integral membrane proteinAquaporin-0 or Major Intrinsic Protein (Aqp0 or MIP).
Ionic Balance in the Lens• A sodium-potassium ATPase pump, an intrinsic membrane protein hydrolyzes ATP, to transport Na+ out and K+ in to the lens. • Na+-K+-pumps are found primarily in the anterior surface of the lens, in the epithelium and outer, immature fiber cells.
Intercellular Communication in the LensThrough gap junctions consisting of connexin 43 in the epithelial cells and Cx-46 and -50 in the fiber cells. MIP (Aqp0) also helps in intercellular communication.
Primary Source of Energy in the LensAnaerobic glycolysis is the primary source of energy in the lens. Pentose phosphate pathway is used in oxidative stress conditions, to replenish NADPH.
Two critical properties of lens crystallins• Should remain water-soluble at high concentrations• Should be stable and stay active for a long time
Two classes of crystallins• Ubiquitous (Present in all vertebrates)
e.g.,-Crystallin and -crystallins• Taxon-specific (Different in different species)
e.g., -crystallin
What is the native molecular mass of -crystallin? Larger than 600kDa; can be as high as 1500-2000kDa. A- and B-crystallins are both around 20kDa monomers. -crystallin is a super-aggregate of these monomers.
CrystallinsAbundant, stable and water-soluble proteins responsible for the transparent and refractive properties of the lens
How is spherical aberration avoided by the lens?
Glass bead in water Fish lens in water
Decreasing gradient of refractive index from the centre to the periphery of the lens resulting from continual lens development minimizes the spherical aberration
- and -crystallins are structurally related. True B-crystallin is a widely and constitutively expressed member of the small heat shock proteins family and is inducible by heat and other forms of stress. True-crystallin tends to be concentrated in the nuclear region of the lens, as it is abundantly expressed early in development. True Most taxon-specific crystallins are oxidoreductases which bind pyridine nucleotides. Reduced nucleotides absorb UV light, protecting the retina from oxidative damage. True In the normal lens, concentrations of sodium are low (~10mMol/L) and potassium, high (~120mMol/L) relative to aqueous humor, which contains high sodium (~150mMol/L) and low potassium (~5mMol/L). True The lens displays a smooth gradient of refractive index, which is lowest in the oldest cells in the center and the highest in the newest cells at the periphery.False. Refractive index is the highest at the center and the lowest at the peripheryA-crystallin has chaperone-like activity, which is absent in the B-crystallin. False. B-crystallin also has chaperone like activity.
True/False
True/False
