Introduction
The rabbit eye has been a common tool used in ophthalmic science for examining the effects of drugs. Its anatomical and physiological resemblance to the human eye makes it the model of choice for testing ocular pharmacology, drug toxicity, and therapy. In this blog, we examine the action of normal saline, epinephrine, atropine sulphate, ephedrine, physostigmine, lignocaine, phenylephrine, pilocarpine, amphetamine, and cocaine on the rabbit eye and also discuss therapeutic as well as toxic effects.
The rabbit eye is a common model in ophthalmic pharmacology to examine drug action on pupil size, intraocular pressure (IOP), aqueous humor dynamics, and tear production. Different autonomic and local anaesthetic drugs affect ocular physiology differently.
Why Rabbits?
Rabbits are popular in ophthalmic studies because of:Large corneal surface area, perfect for topical drug application.
A developed blood-aqueous barrier, as in humans.
Ease of handling and observation of ocular response.
Frequently Investigated Drugs and Their Effects
1. Mydriatics and Cycloplegics
Mydriatic agents produce dilation of the pupils (mydriasis), whereas cycloplegics cause temporary paralysis of the ciliary muscles.Atropine: Produces prolonged mydriasis and cycloplegia. Side effects are dry eye and a rise in intraocular pressure (IOP).
Phenylephrine: A sympathomimetic causing dilation of the pupil independently of accommodation.
Tropicamide: Causes shorter-duration mydriasis and is thus preferred for diagnostic studies.
2. Miotics
These agents cause pupillary constriction and are commonly employed for glaucoma therapy.Pilocarpine: A cholinergic agonist causing miosis and IOP decrease by stimulating aqueous humor outflow. It causes ciliary spasm and discomfort with overuse.
3. Local Anaesthetics
Employed in ocular surgery and diagnostic work.Proparacaine and Tetracaine: Cause transient corneal anesthesia. On repeated use, these drugs can damage the corneal epithelium and delay healing.
4. Anti-glaucoma Drugs
Glaucoma medications affect IOP lowering through various mechanisms.Timolol (Beta blocker): Reduces aqueous humor secretion, thus lowering IOP. Systemic effects like bradycardia may be caused by prolonged use.
Latanoprost (Prostaglandin analog): Increases aqueous humor drainage. Can result in conjunctival hyperemia and iris pigmentation.
Acetazolamide (Carbonic anhydrase inhibitor): Reduces aqueous humor production systemically but can cause metabolic acidosis as a side effect.
5. Anti-Inflammatory Drugs
Used to manage ocular inflammation and post-surgical healing.Corticosteroids (Dexamethasone, Prednisolone): Reduce inflammation but increase the risk of glaucoma and cataracts with prolonged use.
NSAIDs (Ketorolac, Diclofenac): Provide pain relief and control inflammation without the side effects of steroids.
6. Antibiotics and Antifungals
Used to treat ocular infections.Fluoroquinolones (Ciprofloxacin, Moxifloxacin): Broad-spectrum antibacterials are useful against bacterial keratitis.
Natamycin: Fungistat for fungal keratitis but only minimally penetrated into the cornea.
7. Experimental Therapeutic Agents Under Investigation
Gene therapy agents: Employed to treat diseases such as retinal degeneration.Neuroprotective drugs: Investigated in preventing optic nerve injury in models of glaucoma.
Side Effects and Special Considerations
Toxicity: Certain medications induce corneal toxicity after long-term usage.
Systemic Absorption: Some ophthalmic medications systemically absorbed can cause adverse effects.
Species-Specific Responses: The rabbit eye is unique compared to humans in tear chemistry and metabolism, necessitating cautious extrapolation of information.
Effects of Different Drugs on the Rabbit Eye:
1. Normal Saline (0.9% NaCl Solution)
Control Solution: To which other drugs are compared.No Pharmacological Effect: Preserves normal tear film and corneal hydration.
No Alteration in Pupil Size or IOP.
2. Epinephrine (Adrenergic Agonist)
Mild Mydriasis (Pupil Dilation): Stimulates α-receptors, causing slight dilation of the pupil.Reduces IOP: Enhances aqueous humor outflow via the trabecular meshwork.
Conjunctival Hyperaemia: Vasodilation may result in temporary eye redness.
Possible Irritation: May cause transient burning or discomfort.
3. Atropine Sulphate (Anticholinergic Agent)
Strong Mydriasis: Blocks muscarinic receptors, causing prolonged pupil dilation.Cycloplegia (Accommodation Loss): Inhibits the eye from accommodating to near vision.
Raises IOP: Blocks aqueous humor outflow and exacerbates glaucoma risk.
Decreases Tear Secretion: This can be a cause of dry eye.
4. Ephedrine (Indirect Adrenergic Agonist)
Moderate Mydriasis: Stimulates adrenergic receptors indirectly by releasing norepinephrine.Increases Aqueous Humor Secretion: Slight rise in IOP is possible.
Slightly Shorter Duration Than Phenylephrine or Atropine.
5. Physostigmine (Cholinesterase Inhibitor, Parasympathomimetic)
Induces Miosis (Pupil Constriction): Facilitates acetylcholine action, stimulating the sphincter pupillae.Decreases IOP: By enhancing aqueous humor drainage via the trabecular meshwork.
Increases Tear Production: This can lead to excessive lacrimation.
Potential Ciliary Spasm: Can result in brow ache and blurred vision.
6. Lignocaine (Local Aesthetic)
No Significant Effect on Pupil Size or IOP.Corneal Anaesthesia: Prevents sensory nerve conduction, making corneal reflex less sensitive.
Temporary Loss of Blink Reflex: Can cause dry eye if overused.
7. Phenylephrine (Selective Alpha-1 Adrenergic Agonist)
Strong Mydriasis: Acts on α1 receptors, causing pupil dilation without any effect on accommodation.Mild IOP Reduction: Through vasoconstriction that decreases aqueous humor production.
No Impact on Ciliary Muscle: Unlike atropine, it does not produce cycloplegia.
8. Pilocarpine (Cholinergic Agonist, Parasympathomimetic)
Causes Miosis: Causes contraction of the sphincter pupillae, resulting in pupil constriction.Reduces IOP: Through increased trabecular meshwork outflow.
Increases Tear Secretion: Acts on lacrimal glands.
May Cause Blurred Vision and Discomfort Due to Ciliary Spasm.
9. Amphetamine (Indirect Adrenergic Agonist and CNS Stimulant)
Mild to Moderate Mydriasis: Causes release of norepinephrine, dilating the pupils.Increases IOP Slightly: By stimulating aqueous humor production.
Potential Vasoconstriction: May decrease conjunctival redness.
10. Cocaine (Local Aesthetic and Indirect Adrenergic Agonist)
Strong Mydriasis: Inhibits reuptake of norepinephrine, extending sympathetic action.Reduces Tear Production: May produce corneal dryness.
Potential Corneal Toxicity: Prolonged exposure damages epithelial cells.
Mild Rise in IOP.
Conclusion
Varying effects of drugs on pupil diameter, IOP, and tear secretion have been observed in the rabbit eye. Adrenergic drugs such as epinephrine and phenylephrine result in mydriasis and IOP decrease, whereas cholinergic drugs such as pilocarpine and physostigmine produce miosis and a decrease in IOP. Local anaesthetics such as lignocaine essentially offer corneal anaesthesia, whereas drugs like cocaine and amphetamine induce pronounced dilation and potential toxicity. Familiarity with these actions is important both in ophthalmic drug development and in clinical situations.