anatomy and physiology of the optic nerve

8/10/2019 Anatomy and Physiology of the Optic Nerve

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1. Anatomy and Physiology1. Anatomy and Physiologyof the Optic Nerveof the Optic Nerve

Alfredo A. Sadun, MD, PhDAlfredo A. Sadun, MD, PhD

Thornton Professor of VisionThornton Professor of Vision

Doheny Eye InstituteDoheny Eye Institute

Departments of Ophthalmology andDepartments of Ophthalmology andNeurosurgeryNeurosurgery

Keck/USC School of MedicineKeck/USC School of Medicine


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Optic Nerve and AnteriorOptic Nerve and Anterior

Visual PathwaysVisual Pathways

AnatomyAnatomy

PhysiologyPhysiology


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RETINARETINA

9 Layers9 Layers

Anatomical layout (horizontalAnatomical layout (horizontal rapheraphe))

33 functional layersfunctional layers

Photoreceptors (rods and cones)Photoreceptors (rods and cones) Bipolar cells andBipolar cells and integratorsintegrators

Retinal ganglion cellsRetinal ganglion cells


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Original Ramon Y Cajal from Golgi stain


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RETINAL LAYERS

NFL

RGC

IPL

INL

OPL

ONL

IS

OS

RPE

SCLERA


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Why Visual Fields respect Horizontal Raphe:

Cogan, trypsin digest


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Lesions of the optic disc/nerveLesions of the optic disc/nerve

Visual field defect =Visual field defect = arcuatearcuate/central/central

Less than 50% loss no effect on:Less than 50% loss no effect on:

VFVF

VAVA

ContrastContrast

ColorColor Disc appearanceDisc appearance


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1B. Neuro1B. Neuro--retinaretina

((NeuroprotectionNeuroprotection and Apoptosis)and Apoptosis)

Alfredo A. Sadun, MD, PhDAlfredo A. Sadun, MD, PhD

Thornton Professor of VisionThornton Professor of Vision

Doheny Eye InstituteDoheny Eye Institute

Departments of Ophthalmology andDepartments of Ophthalmology andNeurosurgeryNeurosurgery

Keck/USC School of MedicineKeck/USC School of Medicine


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Why Visual Fields respect Horizontal Raphe:

Cogan, trypsin digest


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IfIf NeuroprotectionNeuroprotection = good for= good for

neurons then:neurons then:

Wearing a bicycle helmet isWearing a bicycle helmet isneuroprotectionneuroprotection


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DEATH


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Poor Signaling : Black sail sentPoor Signaling : Black sail sent

AgeusAgeus leaping to his deathleaping to his death


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RGCsRGCs = Neurons= Neurons

Die from a variety of processesDie from a variety of processes

NecrosisNecrosisChromotolysisChromotolysis (cellular breakdown)(cellular breakdown)

Membrane disruptionMembrane disruption

Swelling of peripheralSwelling of peripheral cytosolcytosolNoxious to adjacent cellsNoxious to adjacent cells

Release of glutamateRelease of glutamate

Inflammatory changesInflammatory changesApoptosisApoptosis


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APOPTOSISAPOPTOSIS

Cell suicideCell suicideProgrammed cell deathProgrammed cell death

Energy dependentEnergy dependent

Orchestrated series ofOrchestrated series of

intraintra--cellular eventscellular events

Involution of cell/quietInvolution of cell/quietdeathdeath

Sparing of collateralSparing of collateral

damagedamage


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APOPTOSISAPOPTOSIS

WhatWhats so good about it?s so good about it?

OntogenyOntogeny

Tumor controlTumor controlNeuronal specificityNeuronal specificity


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Mitochondria againMitochondria again

Once free living bacteriaOnce free living bacteria

LynnLynn MargulisMargulis model of synergymodel of synergyIncorporation of ATP factoriesIncorporation of ATP factories

Also a built in TIME BOMBAlso a built in TIME BOMB


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How do retinalHow do retinal

ganglion cells die?ganglion cells die?


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Extra cellularExtra cellular

SignalingSignaling

FASFAS--LigandLigand

TNFTNF

Death domainDeath domain


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MitochondrialMitochondrial

Key lynchKey lynch

--pinpin

Membrane pot.Membrane pot.

affected byaffected by

ROSROS BAXBAX

Stabilized byStabilized by

BCLBCL--22


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Open poresOpen pores

Cytochrome CCytochrome C

releasedreleased

Nuclear gene controlNuclear gene control PP--53 promotes53 promotes

PP--35 blocks35 blocks

ReleaseRelease


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Mechanisms of RGC deathMechanisms of RGC death

IschemiaIschemiaCytotoxicCytotoxic (NMDA)(NMDA)

InflammatoryInflammatory

ProPro--inflammatoryinflammatory

Energy depletionEnergy depletion

ROSROSAxonal compromiseAxonal compromise

AxoplasmicAxoplasmic flowflow

Retrograde degenerationRetrograde degeneration


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AIDS OPTIC NERVEAIDS OPTIC NERVE

Degenerated axonsDegenerated axonsLong standingLong standing

Myelination of debrisMyelination of debris


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AIDS OPTICAIDS OPTIC

NERVENERVE

Axonal deg.Axonal deg.

Various stagesVarious stages


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AIDS OPTIC NERVEAIDS OPTIC NERVE

MacrophageMacrophage

Toxic expression?Toxic expression?


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CYTOKINESCYTOKINES

That can induce apoptosisThat can induce apoptosis TNFTNF

ILIL--11

ILIL--2b2b ILIL--66

IFNIFN--gg

That may mitigate apoptosisThat may mitigate apoptosis

ILIL--1010

NGFNGF


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TNF BINDING TO TNF R1TNF BINDING TO TNF R1Liberation of G proteinsLiberation of G proteins

Causing release ofCausing release of phospholipasesphospholipases

Stimulating the release ofStimulating the release of arachadonicarachadonic a.a.

Elaboration of proteinElaboration of protein kinaseskinasesSecondarily activatingSecondarily activating xanthinexanthine oxidaseoxidase

And reactive oxygen species (ROS)And reactive oxygen species (ROS)


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OPTIC NEUROPATHIESOPTIC NEUROPATHIESHow does glaucoma killHow does glaucoma kill RGCsRGCs??

PressurePressure

IschemiaIschemia

NeurotrophicNeurotrophic factorsfactors

M A I


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Mitochondrial Apoptotic Index

Disease

M n SOD

glutathione

L H O N

ROS

+

-

Compensation

(patient and

tissue specific)

mtDNAc protein

mtTarea

ROS

mtTarea

+

-= MAI

mitochondrion

+

MPTP

Cyt C

Apoptosis

1a

1b

1c

2a

2b

determines patient

penetrance andtissue specificity


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WHERE IS THE BEST PLACE TOWHERE IS THE BEST PLACE TO

BLOCK APOPTOSIS?BLOCK APOPTOSIS?

1) 01) 0--1 hr: blocking TNF or FAS receptors1 hr: blocking TNF or FAS receptors

2) 12) 1--3 hrs: blocking mitochondrial pores3 hrs: blocking mitochondrial pores

3) 33) 3--6 hrs: blocking secondary6 hrs: blocking secondary capsasescapsases

4) 64) 6--8 hrs: DNA fragmentation8 hrs: DNA fragmentation

But processes not serialBut processes not serial

anatomy and physiology of the optic nerve

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