Pharmacology of Nicotine and Effects on the eye

What receptors does nicotine primarily act on in the autonomic nervous system (ANS)?

Nicotinic acetylcholine receptors (nAChRs) present at autonomic ganglia.

How does nicotine affect both branches of the ANS?

Nicotine acts as an agonist, increasing activity in both the sympathetic and parasympathetic branches.

What are the three main classifications of nicotinic acetylcholine receptors?

NM (neuromuscular junctions)

NN (autonomic ganglia)

CNS receptors.

What is the basic structure of nicotinic acetylcholine receptors?

They are pentameric ligand-gated ion channels composed of five subunits.

Name a modifiable risk factor for several ocular conditions.

Smoking.

Which Ocular Conditions is smoking a modifiable risk factor for?

1. Anterior Segment Surface Disorders

2. Glaucoma

3. Diabetic Retinopathy

4. Age-related macular degeneration (AMD)

5. Inflammation (around eye lids)

6. Pupil constriction (pinpoint appearance)

7. Grave’s ophthalmopathy

List four anterior segment surface disorders linked to smoking.

1. Cataracts

2. Dry eye disease

3. Uveitis

4. Corneal damage.

How does smoking exacerbate anterior segment surface disorders?

By causing increased tear break up time, changes in lipid layer composition, and reduced basal tear secretion.

What is the main cause of oxidative damage in cataract formation due to smoking?

Reactive oxygen species (ROS) production.

Which are basically oxygen free radicals

What is a Reactive Oxygen Species

A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell (once again an oxygen free radical)

How does nicotine exposure affect aqueous outflow and glaucoma risk?

It causes vasoconstriction and oxidative stress, reducing aqueous outflow and increasing intraocular pressure (IOP).

How does smoking affect diabetic retinopathy in Type 1 diabetes?

It is associated with an increased risk of diabetic retinopathy and proliferative diabetic retinopathy.

What conflicting effects of smoking have been observed in Type 2 diabetes and diabetic retinopathy?

Some studies show decreased risk, while others show increased risk due to hypertension and tissue hypoxia (lack of oxygen in tissues).

How does smoking contribute to age-related macular degeneration (AMD)?

By causing oxidative damage and promoting neovascularization.

What are two major processes that smoking promotes in AMD and diabetic retinopathy?

Aberrant Angiogenesis (excessive blood vessel growth) and oxidative stress.

Define angiogenesis

The process of forming new blood vessels which is abnormal

It is often associated with AMD and diabetic retinopathy

Problems with the new blood vessels

More fragile vessels

Leakage occurs

Detachment of retinal pigment epithelium

Scarring of macula

Process of Angiogenesis

Endothelial cell proliferation

Adhesion

Migration

Differentiation to capillary tubule structures

Production of new basement membrane around the vessel

Name three angiogenic growth factors upregulated by nicotine.

VEGF-A

Basic fibroblast growth factor (bFGF)

Platelet-derived growth factor (PDGF).

What cytokines and factors are associated with AMD?

VEGF-A

TNF-α

Prostaglandins

Matrix metalloproteinases (MMPs).

Which receptors are present on the choroid and retinal epithelium affected by nicotine?

α3, α5, α7, α9, β1, β3, and β4.

How does nicotine indirectly promote angiogenesis?

By upregulating endothelial nitric oxide synthase (eNOS) and inflammatory cytokines like TNF-α.

What specific antagonists can block the effects of nicotine on nAChRs?

Antagonists targeting α7 and α9 subunits.

How does nicotine increase the risk of Grave’s ophthalmopathy?

By decreasing oxygen in tissues, increasing inflammation, and promoting adipogenesis.

What are the effects of nicotine on pupil size?

Pupil constriction (pinpoint appearance).

How does smoking alter corneal biomechanical properties in glaucoma patients?

It may cause changes in intraocular pressure (IOP) readings that do not reflect true changes.

How does smoking affect tear composition?

It reduces lysozyme concentration in tears, increasing susceptibility to infections.

What type of inflammation is associated with smoking and the eyelids?

Inflammation around the eyelids.

What process leads to retinal pigment epithelium detachment in AMD?

Leakage from fragile new blood vessels formed during aberrant angiogenesis.

Which adhesion molecules are involved in angiogenesis promoted by nicotine?

Integrins and selectins.

What can exacerbate the effects of nicotine in angiogenesis and AMD progression?

Increased production of MMP-2 and MMP-9.

What role do Muller cells play in the retina concerning nicotine’s effects?

Muller cells, which have nAChRs, are involved in retinal inflammation and angiogenesis.

How does nicotine affect blood vessel structure in angiogenesis?

It promotes the production of a new basement membrane around vessels.

What plasma factor is directly proportional to nicotine’s risk effects?

Nicotine plasma concentration.

How does nicotine affect diabetic patients differently depending on co-morbidities?

Co-morbidities like hypertension and hyperlipidemia exacerbate (worsens) its effects on diabetic retinopathy.

What structural difference between NM and NN receptors affects their function?

NM receptors have specific subunits (α1, β1, γ, δ, ε), while NN receptors have a broader range of subunits.

What indirect effect does smoking have on aqueous humor dynamics?

It can alter trabecular meshwork cell health, reducing aqueous outflow.

How does nicotine affect endothelial cell migration in angiogenesis?

It increases endothelial cell adhesion and migration, promoting new vessel formation.

What is the clinical relevance of blocking α7 nAChRs in AMD?

It may reduce aberrant angiogenesis and slow AMD progression.

What are glycosaminoglycans, and how are they related to Grave’s ophthalmopathy?

They are polysacharrides

They are produced in increased amounts due to smoking, contributing to orbital tissue expansion.

Grave’s Ophthalmopathy issue with fat

Increases adipogenesis - Increased volume of orbital fatty connective tissues

How does nicotine affect ocular inflammation in smokers?

By promoting cytokine release and increasing inflammatory responses.

What effect does smoking have on basal tear secretion?

It reduces basal tear secretion, contributing to dry eye disease.

How does nicotine contribute to scar formation in AMD?

By promoting fragile new vessel growth and subsequent leakage and scarring.

Why is nicotine replacement therapy considered less risky than smoking for ocular health?

Because it avoids the harmful effects of smoke, such as oxidative stress and inflammatory damage.