CAL Exercise -Effects of

Drugs on Rabbit’s Eye

Dr Kauser Sayedda
Aim of Experiment
► To demonstrate the effects of drugs on Rabbit’s eye

► Drug is instilled in one eye & its effects are observed

on different parameters of eye and are compared with

those of control eye

contd.
► Parameters-

1. Pupil size

2. Light reflex

3. Corneal reflex

4. State of conjunctival vessels

5. Intraocular pressure/tension
Procedure

► Rabbit is placed in a comfortable environment in rabbit

holder , with head outside in dim light (not in bright light)

► Gently, eye lashes of one eye is trimmed

► Lower eyelid is pulled downwards & drug is instilled in the

pouch created while pressing the medial canthus so that

drug may not be absorbed in systemic circulation

Contd.
► After sometime,(1min, 10min,30min) start examining

the eyes

► First, pupil size is observed- it may be increased or

decreased

► Thereafter other parameters are also observed

MYDRIATICS
Mydriasis

► Increased size of pupil called as- Mydriasis; & the

drug causing it is called mydriatic

► Mydriatics belong to two major groups-

1. Parasympatholytics (anticholinergic)

2. Sympathomimetics (adrenergic)
Contd.

► Prototype drug in anticholinergic group is atropine

► Atropine causes mydriasis –passive

► Light reflex (pupillary reflex) is absent

► Paralysis/loss of accomodation (cycloplegia)

Contd.
► Intraocular pressure may be raised

► Conjuctival vessels are not congested

Mydriasis by anticholinergic drug

► Mydriasis is of passive type

► Caused by relaxation of sphincter pupillae muscle of iris as a

result of blockade of M3 receptors present on sphincter
pupillae.

► M3 receptors can not be stimulated by Acetylcholine ---

circular muscles can not be contracted ---unopposed
contraction of radial muscles of iris leads to increased size of
pupil
Mydriasis by Sympathomimetic drug

► Mydriasis caused by sympathomimetics is Active

mydriasis

► It is due to contraction of radial muscles of iris by

stimulating α1 receptor
Pupillary Light reflex(PLR)

► It is the automatic constriction of the pupil in response to

bright light, which acts to protect the retina and

regulate light intake.

► It is a key diagnostic tool used to assess neurological

function, specifically the optic and oculomotor nerves

Contd.
► The optic nerve or photosensitive ganglionic cells

through the retinohypothalamic tract forms the afferent

limb of PLR , senses the incoming light.

► The Oculomotor nerve is responsible for efferent limb

of PLR, it drives the iris muscles that constrict the

pupil
Contd.
Optic chiasma

► An X-shaped structure, where optic nerves from both

eyes meet and partially cross

► Nasal (medial) nerve fibers from each retina cross to

the opposite (contralateral) optic tract, while temporal

(lateral) fibers stay on the same side

Contd.
► It allows each cerebral hemisphere to receive information

from the contralateral visual field

► Depth Perception: By merging visual data from both

eyes, it facilitates three-dimensional vision

Contd.

► Clinical Relevance: Imaging of this area helps diagnose

pituitary tumors, which, when compressing the chiasma,

typically cause bitemporal hemianopsia (loss of

peripheral vision, also called as Tunnel Vision).

Contd.
Pretectal nuclei

► Acts as the central control for the pupillary light reflex

(PLR), receiving retinal input to mediate pupil
constriction.

► It acts as the afferent relay center, processing light

levels and triggering bilateral pupil contraction via

projections to both Edinger-Westphal nuclei.

Optic chiasma
Terminologies related to PLR

► Left direct PLR is the left pupil's response to light

entering the left eye, the ipsilateral eye

► Involves neural segments 1, 5, and 7. Segment 1 is the

afferent limb, which includes the retina and optic nerve.

Segments 5 and 7 form the efferent limb

Contd.
► Left consensual PLR is the left pupil's indirect response to

light entering the right eye, the contralateral eye

► Involves neural segments 2, 4, and 7. Segment 2 is the

afferent limb. Segments 4 and 7 form the efferent limb.

Contd.
► Right direct PLR is the right pupil's response to light

entering the right eye, the ipsilateral eye.

► Involves neural segments 2, 6, and 8. Segment 2 is the

afferent limb. Segments 6 and 8 form the efferent limb.

Contd.

► Right consensual PLR is the right pupil's indirect response to

light entering the left eye, the contralateral eye.

• Involves neural segments 1, 3, and 8. Segment 1 is the

afferent limb. Segments 3 and 8 form the efferent limb

Consequences of damage at any point in
PLR pathway
► Damage on the left afferent limb (e.g. transection of left

optic nerve, CN II, somewhere between retina and Optic

Chiasma , leaving the rest of the pupillary light reflex

neural pathway on both sides intact will have the

following clinical findings:

Contd.

◦ When the left eye is stimulated by light, neither pupils

constrict. Afferent signals from the left eye cannot pass

through the transected left optic nerve to reach the intact

efferent limb on the left & right both . Thus:

1. Left direct PLR lost

2. Right consensual /indirect PLR lost
Contd.
◦ Direct light reflex of right pupil involves the right optic
nerve and right oculomotor nerve, which are both

intact. Thus:

1. Right direct PLR intact

2. Left Consensual/indirect PLR intact
Contd.
► Damage on the left Oculomotor (e.g. transection of left

oculomotor nerve, CN III, therefore damaging the left

efferent limb) will have the following clinical findings:

Contd.
◦ When the left eye is stimulated by light, left pupil does
not constrict, because the efferent signals cannot pass

from midbrain, through left CN III, to the left pupillary

sphincter. Thus-

1. Left Direct PLR lost

2. Right consensual reflex is intact
Contd.
◦ When light is thrown into right eye, right pupil
constricts. Direct reflex of the right pupil is unaffected,

The right afferent limb, right CN II, and the right

efferent limb, right CN III, are both intact. Thus-

1. The Right direct PLR is intact

2. The Left consensual PLR is lost.

Accomodation reflex

► The near/accommodative response is a three-component

reflex that assist in the redirection of gaze from a

distant to a nearby object.

► It consists of a pupillary constriction, lens

accommodation reflex, and convergence reflex.

Contd.
Afferent pathway for pupillary constriction, lens

accommodation, and convergence:

► Afferent input from the retina is sent to the lateral

geniculate nucleus (thalamus) via the optic tract. Fibers

from the LGN then project to the visual cortex

through optic radiations

Contd.
► Once the visual cortex identifies the need for focus,

signals are sent to the visual association area (Area 19).

From there, the information travels through the internal

capsule to reach the midbrain centers (superior

colliculus and pretectal area), which then trigger

the efferent response (via the Oculomotor Nerve, CN

III
Contd.
► Efferent pathway for pupillary constriction: Efferent

parasympathetic fibers from the E-W nucleus project via

the oculomotor nerve to the ciliary ganglion and then

short ciliary nerves to innervate the iris sphincter muscle

(target 1) to cause pupillary constriction

Contd.
► Efferent pathway for lens accommodation: Efferent

parasympathetic fibers from the E-W nucleus project via the

oculomotor nerve to the ciliary ganglion and then short ciliary

nerves to innervate the ciliary muscle (target 2 ) to cause

contraction. Contraction of the ciliary muscle allows the lens

zonular fibers to relax and the lens to become more globular,

focal length of lens reduced—eyes are accomodated for

near vision
Contd.
► Efferent pathway for convergence: Efferent somatic

fibers from the medial rectus subnucleus of the

oculomotor complex in the midbrain innervate the

bilateral medial rectus muscles to cause convergence

Clinical implications

► Clinical implications include diagnosing neurological

disorders (midbrain lesions, syphilis), neuromuscular

disease (myasthenia gravis), and

determining pharmacological effects.

► Dysfunction causes blurred near vision (presbyopia,

accommodative insufficiency
Contd.
► Argyll robertson pupil : a distinct clinical sign where the

pupils are small, irregular, and do not constrict when

exposed to bright light, but do constrict normally when

focusing on a near object. This phenomenon is known
as light-near dissociation. as in Neurosyphilis

► Neurological dysfunction : Impairment of all three suggests

midbrain lesion, pineal tumours & encephalitis
Contd.
► Oculomotor nerve palsy— loss of accomodation &

convergence & mydriasis

Accomodative anomalies

► Presbyopia: Age related decrease in accomodative

amplitude, causing difficulty with near tasks

► Accomodative insufficiency- A reduction in the ability

to increase lens curvature, often causing headaches and

blurred vision (asthenopia). It can occur in young

individuals .
Contd.
► Accomodative excess- Ciliary muscle spasm, often

resulting in pseudomyopia

• Drug-Induced Deficits: Medications like

anticholinergics, SNRIs, and TCAs can inhibit the reflex,

causing blurred near vision.

Contd.
• Clinical Testing: The reflex is checked by observing the

"near triad" (pupil constriction, convergence, and lens

thickening) when a patient shifts focus from distance to a

near object, such as a finger placed 10 cm from the nose.

Pathological conditions

► Myasthenia gravis: Can cause weakness in convergence

or accommodation

► Glaucoma/cataracts: can affect the reflex

Management strategies

► Correction: Proper refraction plus lenses & alleviate near

work symptoms
Corneal reflex
► The corneal reflex, also known as the blink reflex.

► There is involuntary blinking of the eyelids elicited by

stimulation of the cornea (such as by touching or by a

foreign body), though could result from any peripheral

stimulus.
Contd.
► Stimulation should elicit both a direct and consensual response

(response of the opposite eye). The reflex occurs at a rapid

rate of 0.1 seconds

► The purpose of this reflex is to protect the eyes from foreign

bodies and bright lights (the latter known as the optical
reflex). The blink reflex also occurs when sounds greater than
40–60 dB are made.
Contd.
► The reflex is mediated by:
► The Nasociliary branch of the ophthalmic division (V1) of
the trigeminal nerve (CN V) sensing the stimulus on the
cornea only (afferent fiber)

► The temporal and zygomatic branches of the facial nerve (CN

VII) initiating the motor response (efferent fiber)

► The center (nucleus) is located in the pons of the brainstem .

Corneal reflex damage

► Indicates serious, often permanent, disruption to the –

1. Trigeminal (afferent) or facial (efferent) nerve

pathways,

2. Brainstem lesions,

3. Tumors (like acoustic neuroma), or severe

neurotrophic keratitis..
Clinical implications
► Include an inability to protect the eye, leading to chronic
dry eye, epithelial breakdown, painless corneal ulcers, and

potential vision loss

► Neurological diagnostic tool-

1. Unilateral Absence: Suggests a peripheral lesion of the
trigeminal (V) or facial (VII) nerve.

2. Bilateral Absence: Suggests significant brainstem damage,

deep coma, or profound neurological impairment
Parasympatholytic—Atropine

Parameters Control Eye Treated Eye

Size of pupil Normal Increased

Light Reflex Present Absent

Corneal Reflex Present Present/absent

(dose dependent)
State of Normal Pale/unaffected
Conjunctival
vessels
Intraocular Pressure Normal Increased
Sympathomimetic—Phenylephrine

Parameters Control Eye Treated Eye

Size of pupil Normal Increased

Light Reflex Present Present

Corneal Reflex Present Present

State of Normal Pale

Conjunctival
vessels
Intraocular Pressure Normal Increased
Miotics
Effect of miotics on Rabbit’s Eye
► Miotic –Constriction of pupil

► Decrease in size of pupil

► The drugs having cholinergic (parasympathomimetic)

activity show miosis

► Active and passive miosis

Contd.
► Active miosis ---due to contraction of circular muscles

(constrictor pupillae /sphincter pupillae) of iris by M3

receptors agonists like acetylcholine, pilocarpine

► Passive miosis--- due to relaxation of radial muscles by α

blockers
Contd.
► Physostigmine (anticholinesterase) increases levels of
Acetylcholine by inhibiting its hydrolysis by
Acetylcholinesterase ----thus acts indirectly, excess Ach
acts on M3 receptors of circular muscle of iris---
contraction of circular muscles----miosis

► Effect on light reflex ---present

► Effect on corneal reflex----Present

Contd.
► State of conjuctival vessels—congested

► Acetylcholine or drugs having parasympathomimetic activity

(direct/indirect)-----congested conjuctival blood vessels

► Congestion b’coz of vasodilatation caused by Acetylcholine

---Ach acts on M3 receptors present on endothelium of blood
vessels ---- release of NO
Contd.
► Occupation of receptors by agonist activates the Gq-

PLC-IP3 pathway-----activation of Ca++-calmodulin-

dependent endothelial NO synthase & production of

NO (EDRF)

► NO diffuses to adjacent vascular smooth muscles &

causes them to relax---vasodilatation

Contd.
► If endothelium is damaged as under various

pathophysiological conditions----Ach acts on M3

receptors of smooth muscles causing them to contract

Parasympathomimetic –Pilocarpine ,
Physostigmine (indirectly acting)

Parameters Control Eye Treated Eye

Size of pupil Normal Reduced

Light Reflex Present Present

Corneal Reflex Present Present

State of Normal Congested

Conjunctival
vessels
Intraocular Pressure Normal Reduced
Local Anesthetic
 Effect of local Anaesthetic on Rabbit’s
Eye
► Local anaesthetics –cocaine, procaine, prilocaine

► Size
of pupil----mydriasis (increases levels of
norepinephrine by inhibiting its reuptake)

► NEacts on α1 receptors of radial muscles ----

contraction ---active mydriasis

► Corneal reflex absent b’coz of local anaesthesia

Contd.
► Lightreflex present as parasympathetic division is
intact

► Conjuctival vessels pale, not congested

Local anesthetic-cocaine, procaine

Parameters Control Eye Treated Eye

Size of pupil Normal Unaffected /
Increased
Light Reflex Present Present

Corneal Reflex Present Absent

State of Normal Unaffected

Conjunctival
vessels
Intraocular Pressure Normal Unaffected