Novel roles for the lens in preserving overall ocular health.
Outside the traditional roles of the lens as an important refractive element and a UV filter, it was David Beebe's group that first demonstrated that the lens acts an oxygen sink that protects the tissues of the anterior segment of the eye from oxygen or oxygen metabolites. In this review, we follow on from this work, and present new evidence from our laboratory to demonstrate that the lens serves as a reservoir for the release of the antioxidant glutathione (GSH) into the aqueous humor to provide a source of GSH and/or its precursor amino acids to nearby tissues that interface with the aqueous humor, or to remove toxic metabolites from the eye via the aqueous outflow pathway. In addition to GSH release, our laboratory and others have shown that ATP is released from the lens under hyposmotic conditions to activate purinergic signalling pathways in an autocrine manner to alter lens function. In this review, we raise the idea that ATP and/or its subsequent degradation product adenosine may exert a paracrine function and influence purinergic signalling systems in other tissues to alter aqueous humor outflow. These new secondary roles indicate that the lens is not just a passive optical element, but a highly dynamic and active tissue that interacts with its neighbouring tissues, through modifying the environments in which these tissues function. We believe that the lens actively contributes to the ocular environment and as a consequence, removal of the lens would alter the functionality of neighbouring tissues. We speculate that a long term effect of lens removal may be to inadvertently increase the exposure of anterior tissues of the eye to oxidative stress due to elevated oxygen levels and a reduction in the availability of GSH and purinergic signalling molecules in the aqueous humor. Since cataract surgery is now being performed on younger patients due to our increasing diabetic population, over time, we predict these changes may increase the susceptibility of these tissues to oxidative stress and the incidence of subsequent ocular pathologies. If our view of the lens is correct, the actual loss of the biological lens may have longer term consequences for overall ocular health than currently appreciated.
Department of Physiology, University of Auckland, Auckland, New Zealand; School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand. Electronic address: j.lim@auckland.ac.nz.
Julie C
JC
Lim
Department of Physiology, University of Auckland, Auckland, New Zealand; School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand.
Ankita
A
Umapathy
Department of Physiology, University of Auckland, Auckland, New Zealand; School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand.
Angus C
AC
Grey
School of Optometry and Vision Science, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand.
Ehsan
E
Vaghefi
Department of Physiology, University of Auckland, Auckland, New Zealand; School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand.
Paul J
PJ
Donaldson
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000502:physiology*; D009799:Ocular Physiological Phenomena; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D014129:Trabecular Meshwork / Q000378:metabolism
D000975:Antioxidants; D000255:Adenosine Triphosphate; D005978:Glutathione; D010100:Oxygen
Antioxidant reservoir; Cornea; Lens; Oxidative stress; Oxygen sink; Trabecular meshwork