NV1143 Points to ponder

1. How are retinal cells arranged concerning their position towards the inwards and
outwards of the eyeball?
[10 layers of retina]
- Photoreceptors (Rods and Cones): Located in the outer segments near the RPE.
- Bipolar Cells: Cell bodies in the INL, extending processes into the OPL and IPL.
- Horizontal Cells: Cell bodies in the INL, synapsing in the OPL.
- Amacrine Cells: Cell bodies in the INL, synapsing in the IPL.
- Ganglion Cells: Cell bodies in the GCL, with axons in the NFL extending to form the optic
nerve.

2. Why are the photoreceptors, whose function is to absorb light, located at the very
distal part of the retina?
(a) Maximize light absorption
Light transmitted in straight can directly fall on the photoreceptors so that they can
directly detect light stimuli without interference from other retinal cells. This
maximizes the exposure of the fovea’s cones to the light and the efficiency of signal
transmission for visual processing.

(b) Nutrients and waste exchange

PRs at the very distal part of the retina are close to the choroid and RPE.
This allows metabolically active PRs to have efficient nutrients and O2 supplied by
the choriocapillaries.
It also facilitates the removal of metabolic wastes such as recycling visual pigments
by RPE to choriocapillaris to ensure the retinal health.
3. How do the retinal cones and rods differ morphologically?

Cones Rods
Outer segment Cone-shaped Rod-shaped
Inne segment Larger, more mitochondria Smaller, fewer mitochondria
Length Shorter Longer
Density Densely-packed in central fovea Condentrated in peripheral retina
Photopigments Photopsins (S, M, L-cones) Rhodopsins only
Sensitivity Less sensitive, work best in bright More sensitive
** Why cones are less sensitive in dark condition

Photopigment Sensitivity: Cones contain photopsins that are less sensitive to light compared
to the rhodopsin found in rods. The opsin molecules in cones require higher light intensity
to activate compared to rhodopsin in rods. This higher activation threshold means that
cones are less responsive in low-light conditions where light levels are insufficient to
sufficiently activate their photopigments.

4. How do the three types of retinal cones differ?

** Photopigment, Peak sensitivity, Density, Distribution, Visual function **
They differ by their sensitivity in absorbing different wavelengths of visible light. S-
cones are most sensitive to the light in the blue-violet part of the spectrum, around 437nm.
M-cones are most sensitive at absorbing green, around 533nm. L-cones are most sensitive to
the light in red part, around 564nm.
5. How does the cone distribution differ from the rods throughout the retina?
Cones (4-5M) are densely packed in the fovea, especially M and L-cones. However,
there are no S-cones at all in the central fovea. Towards the periphery of the retina, the
density of cones decreases dramatically. Cones are present in lesser numbers than rods from
2mm from the fovea to the periphery.
Rods are most abundant in a ring ~5mm (12-15deg) from the central fovea, the
retina's peripheral region. They are responsible for scotopic vision, which enhances
sensitivity and peripheral vision in low-light conditions. However, the fovea contains no rods.
No photoreceptors at all at the blind spot / optic disc, because there are a bundle of
axons of ganglion cells that form optic nerve.
6. Describe the process when pigments within the retinal photoreceptors’ discs absorb light.
[PHOTOTRANSDUCTION]

7. In the presence of light, photoreceptors hyperpolarize. What does this mean?

When PRs hyperpolarize in the presence of light, it means that their membrane potential
becomes more negative compared to their resting state. In the dark, PRs have a resting
membrane potential. When light strikes the PRs, phototransduction occurs in which
photopigments in the PRs become activated and undergo a conformational change, leading to
the closure of cGMP Na+ ion channels that are normally open in the dark. These channels
inhibit the influx of sodium (Na⁺) into the PR cells. This reduction in ion influx causes
decrease in the depolarizing current, resulting in hyperpolarization of the PR membrane.
The inside of the PR cell becomes more negative relative to the outside. The
hyperpolarization of photoreceptors reduces the release of Glu from their synaptic terminals
onto bipolar cells.
8. How does the dark current that circulates at the outer segment of photoreceptors
change between the presence and absence of light?

DARK:
In the dark, photoreceptor cells are depolarized due to a continuous influx of (Na⁺) through
cGMP-gated ion channels located in the outer segment membrane. These channels are kept
open by the presence of cGMP, which is synthesized and maintained at high levels in the
dark. The membrane potential is maintained at a depolarized state, which leads to a
continuous release of Glu from the synaptic terminals onto bipolar cells.

LIGHT:
When light strikes the photoreceptor, it activates photopigments located in the outer segment
discs. Activated photopigments initiate a series of reactions that lead to the hydrolysis of
cGMP. Decrease in cGMP levels causes the cGMP-gated ion channels to close, reducing the
influx of Na⁺ into the photoreceptor. Closure of these channels results in a decrease in the
dark current and hyperpolarization of the photoreceptor membrane. At the same time, Glu
release from the synaptic terminals onto bipolar cells inhibited.
9. How are retinal bipolar cells classified?
- contact with PRs, response to Glu and their morphology (size)

10. In what ways can a bipolar cell differ from the other one?
11. In the presence of light, some bipolar cells hyperpolarize, and some depolarize. What
does this mean?
- In the presence of light, hyperpolarization occurs when the bipolar cell’s membrane
potential becomes more negative. It has OFF-centers/sign-conserving. Depolarization
occurs when the bipolar cell’s membrane potential becomes less negative. It has ON-
centers/sign-inverting.
@
- In the light, the photoreceptor is hyperpolarized and Glu release is reduced.
- The lack of Glu at the ionotropic receptor causes the ionic channels in the bipolar
membrane to close. The OFF bipolar cell hyperpolarizes, reducing its release of
Glu.
- When Glu is reduced or no longer present, the lack of Glu at the metabotropic
receptor signals a cGMP cascade, cGMP increases, cGMP-gated cation channels
open, and the ON bipolar depolarizes, which increases its neurotransmitter release.

IN DARK Receptor Cell membrane Bipolar cell

Release Glu ionotropic depolarised OFF
metabotropic hyperpolarised ON

IN LIGHT Receptor Cell membrane Bipolar cell

Reduced Glu ionotropic hyperpolarised OFF
metabotropic depolarised ON
12. In the dark, some bipolar cells hyperpolarize, and some depolarize. What does this mean?
- In the dark, the depolarized bipolar cell has OFF-center/sign-conserving.
Hyperpolarized bipolar cell has ON-centers/sign-inverting.
@
- In the dark, photoreceptor is depolarised and releasing Glu.

- When Glu binds to the ionotropic receptor on a bipolar dendrite, ion channels are
opened in the cell membrane, causing the bipolar cell to depolarize and release
Glu. This is an OFF bipolar because it is depolarized in the dark.

- When Glu binds to the metabotropic receptors on a bipolar dendrite, a decrease

of cGMP occurs, closing ion channels in the cell membrane and causing the
bipolar cell to hyperpolarize, decreasing glutamate release. This is an ON bipolar
because it is hyperpolarized in the dark.

*** The OFF bipolar depolarizes in dark and hyperpolarizes in light.

The ON bipolar depolarizes in light and hyperpolarizes in dark. ***
13. How are retinal ganglion cells (rGCs) classified?
- Morphological characteristics, functional properties

14. Describe the ways an rGC can be categorized differently from another.
(a) Morphological characteristics

(c) Functional properties

ON-center ganglion cell OFF-center ganglion cell
Respond to light increments in center of Respond to light decrements in center of
receptive field receptive field
involved in bright light perception involved in dim light perception
15. The absence of light (dark) excites some rGCs and also inhibits some other rGCs. What
does this mean?

16. The presence of light excites some rGCs and also inhibits some other rGCs. What
does this mean?

Some rGCs are excited by the presence of light, meaning they increase their firing rate in
response to light and become depolarized.
Example: ON-center ganglion cells are excited when light falls on the center of their
receptive field.

Other rGCs are inhibited by light, meaning they decrease their firing rate in response to
light and become hyperpolarized.
Example: OFF-center ganglion cells are inhibited when light falls on the center of their
receptive field. They are activated when light is removed from the center of their receptive
field.