Loss of vision in the ageing eye

Age and Ageing, March, 1997 by A.J. Bron

There is evidence that the lowering of ocular pressure slows down the progression of field loss. Reduction in IOP can be achieved medically or surgically. Most patients are started on medical therapy, using a [Beta]-adrenergic blocker, which reduces aqueous inflow. Progressive optic nerve damage may result from poor compliance, spikes of raised IOP from intermittent dosing, or failure to reduce IOP far enough. There are side effects resulting from systemic absorption-increased airways obstruction in asthmatic patients; decreased exercise tolerance; postural hypotension and falls; and occasional psychiatric disturbances, such as confusion, insomnia and depression.

Surgical therapy by laser trabeculoplasty produces only a 25% fall in IOP, and its effects are of limited duration. The most satisfactory method is surgical trabeculectomy, although this too has its problems [6-9].

In discussion, the importance and some of the difficulties of early detection were stressed, as were the future role of genetic approaches; the gene for one form of autosomal dominant glaucoma has already been located.

The ageing lens and cataract

Dr John Harding (University Research Lecturer, Nuffield Laboratory of Ophthalmology, University of Oxford) said that the unique properties and requirements of the lens make it susceptible to age-related damage. Because it must be transparent, most of its cells have no nuclei or mitochondria, which would absorb or scatter light. In the nucleus of the lens the usual energy-providing system is not present, nor is there any ability to synthesise proteins. This crucial restriction means that the proteins of the lens nucleus remain as they were formed in utero, and are vulnerable to damage by chemical changes (post-translational modification). The lens possesses several mechanisms to protect them.

The first line of defence is a number of small molecules which act as free radical scavengers, and mop up other reactive molecules. An example is glutathione, which protects against oxidation. The lens proteins themselves are physically tough, and [Alpha] and, [Beta]-crystallins have blocked, and thus unreactive, N-terminal amino groups. [Alpha]-crystallin also acts as a molecular chaperone, which inhibits undesirable interactions between proteins, and may preserve their structural and functional properties. It also prevents heat-induced aggregation and glycation-induced inactivation of the enzymes. Glycation is a form of post-translational modification.

Future research should identify the causes and mechanisms of cataract formation more clearly, and lead to drugs that might prevent or delay the progress of cataract. Research should concentrate on the common pathways of cataract formation, including protein modification, loss of glutathione, and loss of enzyme activity such as that of Na-K-ATPase, a most potent ion pump [10, 11].

In the discussion, the question was raised as to why the cornea can remain transparent without chaperones. It was suggested that this was because corneal collagen is a very tough protein, and corneal cells have nuclei which are all actively metabolizing, and thus the cornea has less need of chaperones.