BRUCH’S MEMBRANE

Bruch’s membrane is a five-layer structure that consists of the following: the basement membrane of the retinal pigment epithelium, an inner collagenous zone, a middle elastic layer, an outer collagenous zone, and the basement membrane of the choriocapillaris.

CHOROID

The choroid is the posterior portion of the uveal tract; it extends from the ora serrata to the optic disc. The choroid is derived from mesoderm and neuroectoderm. The choroid contains one of the highest rates of blood

flow in the body and provides blood supply to the retinal pigment epithelium (RPE) and outer retina (to the outer two thirds of the inner nuclear layer). It also is responsible for the dissipation of heat and is largely responsible for the pigmentation/coloration of the fundus.

Blood reaching the choroid travels through the internal carotid artery to the ophthalmic artery and then flows through branches of the ciliary arteries, which include the medial and lateral posterior ciliary arteries, long and short posterior ciliary arteries, and the recurrent branches of the anterior ciliary arteries. The blood then travels through the large and medium-sized choroidal vessels before reaching the choriocapillaris. Venous drainage from the choriocapillaris is mainly through the vortex veins located in the equatorial region of the globe.

The choriocapillaris is the rich capillary layer of the choroid. In the posterior fundus, the choriocapillaris is arranged in a mosaic of lobules with a central precapillary arteriole and peripheral postcapillary venules. The choriocapillaris contains fenestrated capillary walls.

NORMAL RETINAL ADHESION

There is a potential space between the neurosensory retina and the RPE. This is the result of the embryologic development of the eye. During the early stages of ocular development, the optic vesicle folds in on itself, becoming the optic cup. The two tissue layers of the optic cup eventually become the outer pigment epithelial layer and the inner neurosensory retinal layer.

The normal retinal adherence is maintained by several factors including the blood retinal barrier, the metabolic activity of RPE and photoreceptors, retinal and choroidal oxygenation, the mechanical interdigitation of RPE microvilli and photoreceptor outer segments, the interphotoreceptor matrix, various hydrostatic

and osmotic forces, and possibly retinal tamponade of vitreous.

BLOOD-RETINAL BARRIER

The blood-retinal barrier has two components: the inner and outer blood-retinal barriers. The inner blood-retinal barrier is composed of tight junctions between the retinal vascular endothelial cells. The outer blood-retinal barrier is the result of tight junctions between retinal pigment epithelial cells. Both the inner and outer blood-retinal barriers contribute to the normal retinal homeostasis by restricting various permeabilities from the plasma. The blood-retinal barriers may be disrupted by a variety of conditions including ischemia and inflammation.

Bruch's mem:

Basal lamina

Elastic layer

Choriocapillaris

Basal lamina

Bruch’s membrane consists of the basement membrane of the retinal pigment epithelium, an inner collagenous zone, a middle elastic layer, an outer collagenous zone, and the basement membrane of the choriocapillaris.

The choroid is a rich vascular network supplying oxygen and nutrition to the retinal pigment epithelium and outer retina. It is arranged in a lobular pattern.

The vitreous is composed of water, hyaluronic acid, hyalocytes, and type II collagen.

The inner and outer blood retinal barriers are demonstrated in this photomicrograph. The fluorescein is retained within the retinal vessels by the endothelial cell tight junctions and the choriocapillaris by the retinal pigment epithelium. (Reprinted with permission from Elsevier Science. [Eagle RC Jr. Mechanisms of maculopathy. Ophthalmology. 1984;91:613–625].)

PHYSIOLOGY OF THE RETINA

Phototransduction, the conversion of light energy into an electrical signal, occurs as a cascade in three stages: pigment activation, cyclic guanosine monophosphate (cGMP) detection, and hyperpolarization.

The photoreceptor outer segments contain the lightsensitive pigment rhodopsin. Rhodopsin is composed of two parts: a protein called opsin and a molecule of vitamin A aldehyde (retinal). In the dark, the retinal takes the form of 11-cis-retinaldehyde, which is a

bent molecule. A photon of light interacts with the 11-cis-retinaldehyde, causing it to rotate about the 11th carbon atom to become all-trans-retinaldehyde. This molecule is straight. This isomeric change in the retinal atom causes a conformational change in the opsin part of the protein, which surrounds the retinal molecule.

Once light causes the change in confirmation of rhodopsin, which is a large membrane-spanning protein, there is a change in the structure and density of the plasma membrane surrounding the protein. This gives rise to stimulation of a g-protein called transducin. Activation of the pigment molecule leads to a reduction in the plasma concentration of the second messenger molecule, cGMP. The g-protein, transducin, stimulates cGMP phopshodiesterase, which in turn converts cGMP to 5'-GMP. Thus the concentration of cGMP in the cytoplasm is dramatically reduced by light.

The outer segment of the photoreceptor has many sodium channels that are gated by cGMP. The Na+ channels are kept open by high concentrations of cGMP and are therefore open in the dark. When light causes transducin to stimulate conversion of cGMP to 5'-GMP, these Na channels are forced to close.

In the dark Na ions are allowed to move into the outer segment of the photoreceptor through many cGMP-gated sodium channels. This current is balanced by active transport of the Na /K -ATPase pump in the inner segment of the photoreceptor. Thus, in the dark there is an ion current (called the dark current) of Na+ ions from the outer to the inner segment of the photoreceptor that is actively driven by the Na /K -ATPase pump in the inner segment and is passively permitted by cGMP-gated Na channels in the outer segment of the photoreceptor. This current causes a continual depolarization of the plasma membrane at the synaptic terminal part of the photoreceptor, leading to release of neurotransmitters.

In summary, light causes reduction of the concentration of cGMP in the outer segment of the photoreceptor, which in turn closes the sodium channels. Light stops the dark current, which causes the photoreceptor to hyperpolarize (all photoreceptors respond to light with a hyperpolarization). This in turn prevents release of neurotransmitters from the synaptic terminal. It is important to remember that the photoreceptor normally releases neurotransmitter in the dark, when it is not stimulated, and is stopped from releasing neurotransmitter when light stimulates the photoreceptor.

The photoreceptor outer segments contain the lightsensitive pigment rhodopsin. Rhodopsin is composed of two parts: a protein called opsin and a molecule of vitamin A aldehyde (retinal).

The outer segment of the photoreceptor has many sodium channels that are gated by cGMP. In the dark, the high levels of cGMP keep the sodium channels open. This allows for passive inflow of Na+ ions into the outer segment. This current is balanced by active transport of the Na /K -ATPase pump in the inner segment of the photoreceptor. In this depolarized state, neurotransmitter is released from the synaptic terminal. Light causes reduction of the concentration of cGMP, which in turn closes the sodium channels. This causes the photoreceptor to hyperpolarize and decrease neurotransmitter release.

The dark current, mediated by Na ions, flows from the inner segment to the outer segment of the photoreceptor. In the dark, the current flux is highest. The dark sodium current maintains the receptor in a depolarized state. Under the influence of light, the sodium current decreases and the photoreceptor membrane hyperpolarizes.