Adenosine receptors and caffeine in retinopathy of prematurity

Jiang-Fan Chen1, Shuya Zhang1, Rong Zhou2

  • 1Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang, China.

Insights

Adenosine receptor-based therapies offer a promising alternative for treating retinopathy of prematurity (ROP), potentially avoiding side effects of current anti-VEGF treatments. Caffeine shows therapeutic effects in ROP models.

Area of Science:

  • Ophthalmology and Developmental Biology
  • Vascular Biology and Angiogenesis
  • Pharmacology and Therapeutics

Background:

  • Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, stemming from oxygen-induced damage to developing retinal vasculature.
  • Current anti-VEGF therapies for ROP have limitations, including adverse effects on eye growth and retinal vascular development in preterm infants.
  • Hypoxia triggers increased extracellular adenosine and adenosine receptors, presenting a potential therapeutic target for controlling pathological angiogenesis.

Purpose of the Study:

  • To review experimental evidence supporting adenosine receptor-based therapeutic strategies for ROP.
  • To examine the role of adenosine receptor subtypes (A1R, A2AR, A2BR) in ROP development and treatment.
  • To highlight the therapeutic potential of caffeine as an adenosine receptor antagonist for ROP.

Main Methods:

  • Review of experimental evidence on aberrant adenosine signaling in oxygen-induced retinopathy.
  • Analysis of studies using oxygen-induced retinopathy models to investigate adenosine receptor subtypes.
  • Evaluation of clinical and animal evidence for caffeine's therapeutic effect in ROP.

Main Results:

  • Aberrant adenosine signaling is implicated in oxygen-induced retinopathy.
  • Adenosine receptor subtypes play distinct roles in ROP development and response to therapy.
  • Caffeine demonstrates therapeutic potential in preclinical ROP models.

Conclusions:

  • Adenosine receptor-based strategies offer a targeted approach to control pathological angiogenesis in ROP without compromising normal vascular development.
  • Caffeine, a non-selective adenosine receptor antagonist, shows promise for ROP treatment.
  • Adenosine receptor and caffeine-based therapies hold translational potential for ROP and other proliferative retinopathies.

Related Concept Videos

Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
4.2K
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
3.1K
Adrenergic Agonists: Indirect-Acting Agents01:25

Adrenergic Agonists: Indirect-Acting Agents

Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
2.9K
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
2.2K
Adrenergic Receptors (Adrenoceptors): Classification01:27

Adrenergic Receptors (Adrenoceptors): Classification

Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors,...
5.4K
Drugs Affecting Neurotransmitter Release or Uptake01:21

Drugs Affecting Neurotransmitter Release or Uptake

Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
1.7K