Metabolic Support of Photoreceptors - Ocular Physiology Spring 2025

mueller cells

Cells that have a supportive function in the retina, regulate and maintains retinal vasculature, metabolism and transport of glucose, and helps protect the retina from oxidative stress

-regulates and maintains retinal vasculature

-metabolism and transport of glucose

-neurotransmitter metabolism

-helps protect the retina from oxidative stress (glutathione production)

-ionic/pH homeostasis

-K+/Cl-/water import & export

-CO2 regulation

-light conduit

What functions of the retina do Mueller cells support?

retinal capillaries

Mueller cells ensheath what?

mechanical, metabolic

Muller cells have ____ and _____ support of the retinal nuerons

enhance barrier function of endothelial cells

Muller cells secrete factors that do what?

angiogenic

Muller cells are anti-________

endothelial cell proliferation

What do Muller cells inhibit?

anti-angiogenic factors

What do Muller cells secrete?

no -- neovascularization occurs toward the vitreous and not within the retina (even during diabetic retinopathy)

D/t the anti-angiogenic factors that Muller cells secrete, will neovascularization occur in the retina?

glycolysis and aerobic respiration

For retinal function, the retina requires both ____ and _____

lactate

Most of the glucose utilized by the retina is converted to what?

yes

Do the retinal arteries take in large amounts of glucose?:

in the retina

What is the only location in the eye where glycogen is produced from glucose?

Muller

Glucose is converted to lactate in _____ cells

lactate dehydrogenase

______ converts the lactate back to pyruvate for use in oxidative phosphorylation in photoreceptors

yes

Glucose is converted to lactate in Muller cells. Is lactate also concerted to glucose in Muller cells?

converted to glycogen or transporter to inner retinal neurons

What happens to glucose in Muller cells?

extracellular glutamate

Muller cells take up what?

1) Prevents lateral spread of glutamate signal to neighboring synapses

2) Modifies the synaptic response (important for regulating the amplitude and duration of ganglion cell action potential)

3) Prevents glutamate induced neurotoxicity

What are the glutamate uptake functions of Muller cells? Why is this function important?

apoptosis (cell death) by triggering the release of calcium ion storage

Too much glutamate in the retina can cause what?

inner plexiform synapses

Muller cells take up a large percentage of the extracellular glutamate derived from __________

photoreceptors (although some by muller cells too)

Most of the photoreceptor synapse glutamate is taken up by what structure in the retina?

GLAST (Glutamate Aspartate Transporter)

Glutamate is transported into Muller cells by _____ transporters

sodium

GLAST transporters utilize the _____ gradient for glutamate transport

glutamine

Muller cells rapidly convert most of the glutamate to what?

glutamine synthetase

Glutamate ---> glutamine in the Muller cells uses what enzyme?

NH4+ (ammonia) and ATP

What 2 substances are needed for glutamine synthesis?

neutral amino acid transporters

Glutamine is transported back to retinal neurons via _______ transporters in the membranes of the Muller cell and retinal neuron cells

NH4+

What is a biproduct of glutamate synthesis in retinal neurons?

to generate glutamate

How do retinal neurons utilize glutamine and the enzyme glutaminase?

from Mueller cells

Glutamine in bipolar cells and inner retinal neurons is almost exclusively from what source?

small

Photoreceptors derive a (large/small) amount of glutamine from Muller cells

glutamine in Muller cells

**increase in NH4+ = increase in glutamine synthesis

NH4+ levels dictate production of what?

GABA (Gamma Amino Butyric Acid)

The major inhibitory neurotransmitter in the vertebrate retina

to process signal to retinal ganglion cells

What is the function of GABA in the retina?

via a Na+/Cl- ion dependent co-transporter (GAT)

How do Muller cells take up GABA?

glutamate

GABA is converted to ______ in the Muller cell via GABA transaminase

The Inner blood retinal barrier

What is necessary to maintain a stable ionic environment to ensure proper function of the specialized environment of the retina?

Endothelial cells

Where are blood vessels present in the retina?

no fenestrations -- tight junctions are found between the endothelial cells

Are there fenestrations of the retinal endothelial cells where blood vessels are present in the retina?

GLUT1 -- transcellularly

In the endothelial cells of the retina, glucose is transported via _______

yes

Do the retinal arteries have a distinct structure?

-endothelium

-3 layers of smooth muscle cells

-astrocytes/Muller cells ensheath the superficial vessels

-muller cells ensheath outer plexuses

What structures compose the Retinal Arteries?

bloodflow (intrinsic ability for vasoconstriction and vasodilation)

The arterial structure of the retina facilitates autoregulation of what?

no

Is there any autonomic supply to the retinal blood vessels?

necessary to maintain a stable ionic environment to ensure proper function of the specialized environment of the retina

What is the outer blood retinal barrier necessary for?

tight junctions between the RPE cells

What does the outer blood retinal barrier consist of?

no -- non-leaky tight junctions are present

Is there any paracellular transport between RPE cells?

nutrients, vit A

What is transported transcellularly across the RPE membrane?

yes

Are the blood vessels of the choriocapillaris fenestrated?

allows glucose and other nutrients to diffuse more freely but need to pass transcellularly throught the RPE

What is the importance of fenestrated choriocapillaris blood vessels?

retina

What has the highest O2 consumption rate of any tissue in the body?

used for glycolysis and converted to lactate

Most glucose of the retina is used for what? Converted to what?

yes, utilizes all available O2 for aerobic respiration

In the dark, does the retina utilize its O2?

-retinal vessels

-choroidal vessels

Where is the oxygen supply for the retina from?

near the choroidal vasculature

Where is the highest pO2 in the retina?

near the photoreceptors

Where is there a steep drop in pO2 in the retina?

energy demands of photoreceptors are so high that all O2 from the choroid is utilized

Why is the pO2 low near the photoreceptors?

true

True or False:

O2 levels in the retina change with light conditions

less O2

Will the retina need more O2 or less O2 in the light?

more O2

Will the retina need more O2 or less O2 in the dark?

Higher rate of aerobic metabolism in the dark

Why does the retina need more O2 in the dark?

-NKA

-generation of GTP (by guanylyl cyclase)

What process(es) have the highest metabolic demand for energy in the retina?

yes

Is the energy demand of the retinal cells altered with illuminated states of the photoreceptors?

decreased

With illuminated photoreceptors, is there an increased or decreased need for NKA?

increased

With non-illuminated photoreceptors, is there an increased or decreased need for NKA?

increased (for the recovery phase)

With illuminated photoreceptors, is there an increased or decreased need for guanylyl cyclase?

decreased need

With non-illuminated photoreceptors, is there an increased or decreased need for guanylyl cyclase?

non-illuminated PR; illuminated PR

The energy requirement for ______ outweighs the energy requirement for ______

flickering

A _____ light causes the retina to maximize its energy usage

an increase in demand of energy from the RGCs, triggers vascular response in retinal vasculature

Why does a flickering light cause the retina to maximize its energy usage?

no

Is there neural innervation of the retinal vasculature or optic nerve head vessels?

rely on local vascular control

What do the retinal vasculature or optic nerve head vessels rely on to match metabolic demand?

signaling pathways

Vascular endothelial cells of retinal vasculature and optic nerve head vessels respond to what?

glia (astrocytes/muller too)

______ can mediate vasomotor responses in retinal vasculature

perfusion pressure -- to maintain constant blood flow to retina and optic nerve

What does the vasomotor system of the retinal vasculature and optic nerve head vessels respond to?

outer

reduction in blood oxygen preferentially affects the ____ retina

causes vasodilation in the retinal vessels and increases blood flow due to release of retinal lactate and endothelium derived nitric oxide

Hypoxia of the retina causes what?

retinal pO2 will remain about the same to a point due to compensatory vasodilation. it will drop once a certain minimal threshold is reached

With hypoxia, will pO2 remain about the same? Why? When will pO2 drop?

choroid

retinal tissue pO2 near the ____ drops linearly with a decrease in arterial pO2 because of the lack of autoregulation function in response to hypoxia

vasoconstriction

Hyperoxia causes ____ of the retinal arterioles

no -- therefore O2 will be higher in the outer retina near the choroid in hyperoxic conditions due to a lack of compensatory vasomotor response

does the choroid blood flow change with increase in pO2 in the retina?

-nitric oxide (NO)

-prostaglandins (PG)

-lactate (stimulating the release of NO and PGs)

What substances play a role in tone relaxing (vasodilation) of retinal blood vessels?

-endothelin-1 (ET-1)

-pericytes express endothelin receptors and respond to ET1 and contract retinal arterioles

What substances play a role in tone contracting (vasoconstriction) of retinal blood vessels?

sympathetic

_____ stimulation reduces choroidal blood flow

-mediated by vasoconstrictive alpha-receptors in smooth muscle cells

-stimulated by the neurotransmitter neuropeptide Y (NPY), a vasoconstricting neurotransmitter

Why does sympathetic stimulation reduce choroidal blood flow?

parasympathetic

_____ stimulation increases choroidal blood flow

-mediated by vasodilation

-stimulated by acetylcholine, vasoactive intestinal peptide (VIP), PACAP, and NO

Why does parasympathetic stimulation increase choroidal blood flow?