X-Message-Number: 27879 Date: Fri, 28 Apr 2006 10:31:31 -0700 (PDT) From: Doug Skrecky <> Subject: presbyopia - the bane of age [Although the human lens grows thicker with age, eye muscles also grow stronger to compensate. The main cause of presbyopia appears to be due to a large increase in lens stiffness driven by an age-associated accumulation of glucosepane crosslinks. The first company to patent eyedrops with glucosepane breakers, as a cure for presbyopia stands to make billions. Young people may not realize this, but presbyopia is a universal scourge in those over 50 years of age. The market for eyedrops effective in treating presbyopia is very, very large.] Ophthalmic Res. 2006 Jan 3;38(3):137-148 [Epub ahead of print] Presbyopia: The First Stage of Nuclear Cataract? Presbyopia, the inability to accommodate, affects almost everyone at middle age. Recently, it has been shown that there is a massive increase in the stiffness(1) of the lens with age and, since the shape of the lens must change during accommodation, this could provide an explanation for presbyopia. In this review, we propose that presbyopia may be the earliest observable symptom of age-related nuclear (ARN) cataract. ARN cataract is a major cause of world blindness. The genesis of ARN cataract can be traced to the onset of a barrier within the lens at middle age. This barrier restricts the ability of small molecules, such as antioxidants, to penetrate into the centre of the lens leaving the proteins in this region susceptible to oxidation and post-translational modification. Major protein oxidation and colouration are the hallmarks of ARN cataract. We postulate that the onset of the barrier, and the hardening of the nucleus, are intimately linked. Specifically, we propose that progressive age-dependent hardening of the lens nucleus may be responsible for both presbyopia and ARN cataract. Prog Retin Eye Res. 2005 May;24(3):379-93. Epub 2004 Dec 19. The mechanism of presbyopia. Accommodation in humans refers to the ability of the lens to change shape in order to bring near objects into focus. Accommodative loss begins during childhood, with symptomatic presbyopia, or presbyopia that affects one's day to day activities, striking during midlife. While symptomatic presbyopia has traditionally been treated with reading glasses or contact lenses, a number of surgical interventions and devices are being actively developed in an attempt to restore at least some level of accommodation. This is occurring at a time when the underlying cause of presbyopia remains unknown, and even the mechanism of accommodation is occasionally debated. While Helmholtz' theory regarding the mechanism of accommodation is generally accepted with regard to broad issues, additional details continue to emerge. Age-related changes in anterior segment structures associated with accommodation have been documented, often through in vitro and/or rhesus monkey studies. A review of these findings suggests that presbyopia develops very differently in humans compared to non-human primates. Focusing on non-invasive in vivo human imaging technologies, including Scheimpflug photography and high-resolution magnetic resonance imaging (MRI), the data suggest that the human uveal tract acts as a unit in response to age-related increasing lens thickness and strongly implicates lifelong lens growth as the causal factor in the development of presbyopia. Mol Vis. 2004 Dec 16;10:956-63. Massive increase in the stiffness of the human lens nucleus with age: the basis for presbyopia? PURPOSE: To determine the stiffness of different regions of human lenses as a function of age, and to correlate the biophysical measurements in the lens center with nuclear water content. METHODS: A custom made probe fitted to a dynamic mechanical analyzer was employed to measure stiffness values at 1 mm increments across equatorial sections of individual human lenses. Thermogravimetric analysis was used to determine the percentage water content in the nuclei of human lenses. RESULTS: There was a pronounced increase in lens stiffness over the age range from 14 to 78. In the nucleus, stiffness values varied almost 1,000 fold over this age range, with the largest change observed in lenses between the ages of 20 to 60. Nuclear stiffness values increased on average by a factor of 450. By contrast, in the cortex the average increase in stiffness was approximately 20 fold over this same time period. In lenses younger than age 30, the nucleus was found to be softer than the cortex. This was true for all six lenses examined. In contrast all lenses older than 30 were characterized by having nuclear values higher than those of the cortex. In lenses over the age of 50, the lens nucleus was typically an order of magnitude more rigid than that of the cortex. The crossover age, when the cortical and nuclear stiffness values were similar, was in the 30s. There was no significant change in the water content of the human lens nucleus from age 13 to age 82. CONCLUSIONS: There is a marked increase in the stiffness of the human lens with age. This is most pronounced in the nucleus. Since in vivo data indicate that the nucleus must change shape significantly during accommodation, it is highly likely that these measured changes in physical properties will markedly diminish the ability of the lens to accommodate, and thus may be a major contributing factor to presbyopia. Since there was no measurable difference in the water contents of the nuclear regions of the lenses, this marked increase in stiffness is not due to compaction of the lens nucleus. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27879