The fundus and retina

• Summary
• Retinal topography
• Layers of the retina
• Cells of the retina
• RPE cells
• Photoreceptors
• Bipolar cells
• Ganglion cells
• Horizontal cells
• Amacrine cells
• Retinal glial cells
• Blood supply of the retina
• Vitreous body
• References
• Author(s)

Summary

The fundus is the inside, back surface of the eye. It is made up of the retina, macula, optic disc, fovea, and blood vessels. In this article we will break down the anatomy of the fundus, in addition to the vitreous body and optic nerve.

Retinal topography

The retina represents the inner layer of the three coats of the eye, and it’s primary function is to convert light into neural impulses which are transmitted to the brain.

We can divide the retina into two main parts: the inner neurosensory retina (which develops from the inner layer of the neuro-ectoderm), and the retinal pigment epithelium, or RPE, (which develops from the outer layer of the neuro-ectoderm). The RPE is poorly adherent to the neurosensory retina resulting in a potential space between them: the subretinal space. The retina has it’s anterior attachment to the ora serrata, and attaches to the optic nerve head posteriorly.

At the external surface of the retina is the Bruch’s membrane, the innermost layer of the choroid. At the internal aspect, we have the vitreous.

The human retina measures 32 mm from ora to ora, with a surface area of 1,100 mm2, and an average thickness of 200 um, which increases around the optic nerve and macula, and decreases around the ora serrata and fovea. It can be divided topographically into the following areas:

• Area centralis: a zone measuring around 5.5 mm, between the superior and inferior temporal arteries. Also known as the ‘posterior pole’. It contains the following structures:
• Macula lutea: a 5 mm diameter area, which lies 3mm lateral to the optic disc, corresponding to 15 degrees of the visual fields. It’s main function is colour vision.
• Fovea: a 1.5 mm diameter area which marks the centre of the macula lutea, located 4 mm temporal to the optic disc and 0.8mm below the horizontal meridian, corresponding to 5 degrees of the visual field.
• Foveola: a 0.35 mm diameter depression at the centre of the fovea where the retina thins, representing 1 degree of the visual field.
• Optic disc: lies 3mm medial to the center of the macula (the fovea). The retinal layers here are disrupted by the ganglion cell axons piercing the sclera to enter the optic nerve, therefore this is known as the blind spot.
• Equator: this is an imaginary circular line drawn through the ampullae of the vortex veins, dilations of the vortex veins which the choroidal veins drain into, situated around 15 mm from the limbus.
• Peripheral retina: this is the area outside of the area centralis, making up 95% of the retina. The peripheral retina is the thinnest (110-140 micrometres).

Layers of the retina

The retina is made up of 10 layers:

1. Retinal pigment epithelium
2. Photoreceptor layer
3. External limiting membrane
4. Outer nuclear layer
5. Outer plexiform layer
6. Inner nuclear layer
7. Inner plexiform layer
8. Ganglion cell layer 
9. Nerve fiber layer
10. Internal limiting membrane

Retinal pigment epithelium: consists of a single layer of hexagonal epithelial cells that lie between Bruch’s membrane and the neurosensory retina. There is a potential space between RPE and neurosensory retina, known as subretinal space. Absence of specialized molecules like laminin and fibronectin, lack of junctional complexes between RPE cells and photoreceptors are responsible for this loose attachment of RPE cells to the photoreceptors. The RPE extends from the optic nerve to the ora serrata and is continuous with the ciliary body pigment epithelium.

Photoreceptor layer: this layer only contains the photosensitive part of rods and cones and not the cell bodies and inner processes (see later description of the photoreceptor cells). In the central fovea the photoreceptor layer has no rods, and only cones sensitive to green light and red light.

External limiting membrane: this is a thin network composed of ‘zonula adherens’ junctions, photoreceptor cells and Muller glial cells. It is through these fenestration that the processes of the rods and cones pass, acting as a metabolic barrier and filtering out large molecules.

Outer nuclear layer: the outer nuclear layer consists of the rod and cone nuclei, (hence the name!). In the peripheral retina there are more rod nuclei, whilst in the fovea we exclusively have cone nuclei.

Outer plexiform layer: this layer contains branching processes and synapses of the horizontal cells and bipolar cells, as well as the inner fibres of the photoreceptors, and lies between the two nuclear layers.

Inner nuclear layer: this layer contains nuclei of horizontal cells, and many different types of bipolar cells, amacrine cells and Müller cells.

Inner plexiform layer: this layer houses the processes and synapses of the cells in the inner nuclear layer (bipolar and amacrine) and ganglion cells. It is also in this layer that we have the synapse between the second-order and third-order neurons of the visual pathway: the bipolar cells with the ganglion cells.

Ganglion cell layer: this is the innermost layer of cell nuclei. The ganglion cells send a single axon which eventually forms the optic nerve, and is the only layer than is continuous across the optic nerve head.

Nerve fibre layer: this layer contains axons of the ganglion cells which turn 90 degrees before running parallel to the surface of the retina and emerge out as the optic nerve.

Inner limiting membrane: this is the innermost layer of the retina, made up of extensions of Muller cells covered by a basement membrane.

Near the ora serrata, the anterior attachment of the retina, the make-up of the retinal layers considerably changes. The inner and outer nuclear layers merge and we see a decrease in the photoreceptor, ganglion and nerve fibre layers. The inner limiting membrane merges with the vitreous base, and the external limiting membrane continues into the ciliary body representing a junction between the pigmented and non pigmented epithelium. What remains of the sensory retina continues as the non-pigmented epithelium of the ciliary body, whilst remnants of the RPE end up as the pigmented epithelium of the ciliary body.

Cells of the retina

Three main cell types:

1. Photoreceptors (sensory receptors)
2. Bipolar cells (first order cells)
3. Ganglion cells (second order neurons)

These carry neural signals in a three step pathway through the retinal layers.

Other cells include:

4) RPE cells

5) Horizontal cells

6) Amacrine cells

7) Glial cells

RPE cells

The cuboidal epithelial cells situated behind the photoreceptors and lying against the Bruch’s membrane. Their apical surface, adjacent to the photoreceptors, has microvilli that surround the tip of the photoreceptor. Their basal surface is attached to Bruch’s membrane by fibronectin Type IV collagen, and other proteins. The main functions of the RPE cells are:

1. Absorb light passing through the retina
2. Help in the regeneration of visual pigments
3. Form the outer blood-ocular barrier
4. Maintain the sub-retinal space
5. Phagocytose the outer segment of the photoreceptor
6. Help with healing and scar tissue formation

Retinal pigment epithelium cells contain melanin and lipofuscin, and it is the variable presence of melanin in these cells that creates the typical patterned fundus appearance (with more pigment in the peripheral retina and less around the macula). It is the melanin that provides protection through absorbing the more damaging wavelengths of visible light.

Photoreceptors

There are two types of photoreceptor: rods and cones.

Rods: responsible for vision at low light levels and provide low spatial acuity (scotopic vision). Rods are absent at the fovea and increase in number towards the periphery, before reducing in number again at the extreme periphery. They contain rhodopsin, have a high regenerative power, are smaller in size and have a slow response speed.

Cones: are active at higher light levels (photopic vision) and provide high spatial acuity. They are capable of colour vision and have increased density near the macula. They contain photopsin, have a low regenerative power, are larger in size and have a faster response.

Each rod consists of an outer segment made up of a stack of membraneous discs, which contain rhodopsin, the visual pigment molecule responsible for the conversion of light into a neural signal. In the cone outer segment, rather than discs the cell membrane makes up layers, which contain the pigment photopsin instead.

The inner segment contains the mitochondria and other organelles. The inner fibre of the photoreceptor is an axonal process which ends in specialised synaptic terminals that meet with bipolar dendrites and horizontal cell processes.

Bipolar cells

These cells transmit information from the photoreceptors to the ganglion cells. They receive information either directly from photoreceptors, or indirectly through the horizontal cells. Their cell bodies lie in the inner nuclear layer. Single or multiple dendrites synapse with the photoreceptors, whilst their single axon synapses with ganglion and amacrine cells. There are two main ypes of bipolar cells, both of which receive the glutamate neurotransmitter, but the ON-center bipolar cells will depolarize, whereas the OFF-center bipolar cells will hyperpolarize. This arrangement helps provide spatial processing of the visual input derived from the photoreceptor cells.

Ganglion cells

These are the third order neurons, receiving input from the photoreceptors via the bipolar and amacrine cells, in other words, the dendrites of these ganglion cells synapse with the axons of bipolar and amacrine cells. The single axon of these ganglion cells form the nerve fibre layer on the innermost surface of the retina, which then leaves the eye as the optic nerve. At this point the fibres are unmyelinated, however as they come out from the eye through the lamina cribrosa, they become myelinated with oligodendrocytes.

Horizontal cells

These cells lie horizontally and parallel to the surface of the retina, close to the synaptic terminal processes of the photoreceptors. They synapse with the photoreceptors, bipolar cells, and other horizontal cells. They use inhibitory GABA and provide inhibitory feedback to the photoreceptor cells and bipolar cells.

Amacrine cells

Amacrine cells are interneurons found close to the ganglion cells. Like horizontal cells, amacrine cells work laterally, but whilst horizontal cells are connected to the output of rod and cone cells, amacrine cells mostly affect the output from bipolar cells, and are mainly found in the inner plexiform layer mostly.

Retinal glial cells

Glial cells are those that surround the neurons and provide support for them. They include Muller cells and astrocytes.

Blood supply of the retina

The retina has a dual blood supply, with the outer layers receiving blood from the choroidal circulation and the inner layers from the post retinal blood vessels of the central retinal vessels. The retinal circulation exclusively supplies retina up to the inner nuclear layer. The outer plexiform layer is supplied by both circulations.

The central retinal artery travels in, or beside, the optic nerve as it pierces the sclera before branching, usually into four main branches, to supply the layers of the inner retina up to the inner nuclear layer. The four branches of the central retinal artery are the upper and lower nasal and the upper and lower temporal arteries. This network forms two capillary networks within the layers of the retina- the superficial network (which is present in the nerve fibre layer, or in the ganglion layer) and a deeper one which is in the inner nuclear layer.

The short posterior ciliary arteries pierce the sclera around the optic nerve then branch to form the arterioles of the choroid, supplying the choroid as far as the equator, and the overlying retina to a depth of about 130 μm, including the retinal pigment epithelium and up to the outer part of the inner nuclear layer. After the arteries pierce the sclera they fan out to form the three vascular layers in the choroid: outer, medial and inner layers (with the outer being most scleral, and the inner, the choriocapillaris, against the Bruch’s membrane). The choriocapillaris lobules drain into venules that join the larger venules that coalesce into the 4-5 vortex veins that pierce the sclera at the equator.

There are some capillary free zones in the retina - these include the foveal avascular zone, an area of approximately 0.5 mm in diameter around all retinal vessels, and in the peripheral retina around 1mm near the ora serrata.

Comparing the retinal and choroidal circulation:

Vitreous body

The vitreous is the transparent gel, comprising around 80% of the total volume of the globe. It is shaped as a sphere with a depression anteriorly, known as the lenticular fossa or hyaloid fossa, which supports the lens. It is supported through various adhesions to the vitreous base, optic disc, the major vessels, and the macula. The vitreous has it’s strongest adhesion at it’s base, a band of 4 to 6 mm width which lies on the posterior aspect of the pars plana and adjacent anterior aspect of the ora serrata. It is here that the vitreous fibres strongly join to the basement membrane of the non-pigmented epithelium of the cilliary body and internal limiting membrane of the periphery of the retina. The vitreous not only offers support to the structures within the eye but also helps maintain the transparency of the media.

We can divide the vitreous into an outer zone and a central zone. The outer cortical zone is richer in collagen, whilst the central zone is more liquid with less collagen. The centre of the vitreous is traversed by a canal known as the hyaloid canal, which takes an ‘S’ shaped course extending from the posterior surface of the lens to the optic nerve head. This represents the embryological remnant of the hyaloid artery.

References

1. Kiel, Jeffrey W. ‘Anatomy’. The Ocular Circulation, Morgan & Claypool Life Sciences, 2010. www.ncbi.nlm.nih.gov, https://www.ncbi.nlm.nih.gov/books/NBK53329/.
2. Simple Anatomy of the Retina by Helga Kolb – Webvision. https://webvision.med.utah.edu/book/part-i-foundations/simple-anatomy-of-the-retina/. Accessed 23 Jan. 2025.
3. Riva, Charles E., and Leopold Schmetterer. ‘Chapter 16 - Microcirculation of the Ocular Fundus’. Microcirculation (Second Edition), edited by Ronald F. Tuma et al., Academic Press, 2008, pp. 735–65. ScienceDirect, https://doi.org/10.1016/B978-0-12-374530-9.00018-8.

Author(s)

Dr Sara Memon

Sara is the Co-Founder of Ophtnotes. She is a doctor who graduated from UCL Medical School in London. She won the Allen Goldsmith Prize in Ophthalmology. Sara is also the co-founder of PAMSA: an organisation linking doctors and medical students of Pakistani origin. She’s especially passionate about teaching and education, having presented a workshop she designed herself at the 2019 Annual GMC Conference.

Published: 4/6/22

Last updated: 23/1/25