Light damage to the retina: an historical approach.

A brief review of retinal light damage is presented. Thermal damage requires a local rise in temperature of at least 10 °C, causing an instant denaturation of proteins. The primary absorber is melanin. Photochemical damage occurs at body temperature and involves cellular damage by reactive forms of oxygen. The photosensitizers are photoproducts of the visual pigments. First indications that non-thermal damage might exist, in particular in the case of eclipse blindness, was presented by Vos in 1962. Attribution thereof to photochemical action was presented in 1966 by Noell et al who also measured the first action spectrum, in rat. It turned out to be identical to the absorption spectrum of rhodopsin. However, in 1976 and 1982 Ham et al found a quite different spectrum in monkeys, peaking at short wavelengths. The latter spectrum, but not the former, was confirmed since in numerous publications with animal models including rat. In ophthalmological practice a 'sunburn' was at first the only complaint caused by light damage. To avoid this, patients with dilated pupils should always be advised to wear sunglasses. Since the invention of the laser accidents have been reported, the most recent development is youth playfully pointing a strong laser pen in their eyes with marked consequences. The operation microscope and endoilluminators should always be used as brief as possible to avoid photochemical damage. Arguments for implant lenses that block not only the UV but also part of the visible spectrum seem too weak to justify extra costs.

Radiation Research Society. 1952-2002. Historical and current highlights in radiation biology: has anything important been learned by irradiating cells?

Around 30 years ago, a very prominent molecular biologist confidently proclaimed that nothing of fundamental importance has ever been learned by irradiating cells! The poor man obviously did not know about discoveries such as DNA repair, mutagenesis, connections between mutagenesis and carcinogenesis, genomic instability, transposable genetic elements, cell cycle checkpoints, or lines of evidence historically linking the genetic material with nucleic acids, or origins of the subject of oxidative stress in organisms, to name a few things of fundamental importance learned by irradiating cells that were well known even at that time. Early radiation studies were, quite naturally, phenomenological. They led to the realization that radiations could cause pronounced biological effects. This was followed by an accelerating expansion of investigations of the nature of these radiobiological phenomena, the beginnings of studies aimed toward better understanding the underlying mechanisms, and a better appreciation of the far-reaching implications for biology, and for society in general. Areas of principal importance included acute tissue and tumor responses for applications in medicine, whole-body radiation effects in plants and animals, radiation genetics and cytogenetics, mutagenesis, carcinogenesis, cellular radiation responses including cell reproductive death, cell cycle effects and checkpoint responses, underlying molecular targets leading to biological effects, DNA repair, and the genetic control of radiosensitivity. This review summarizes some of the highlights in these areas, and points to numerous examples where indeed, many things of considerable fundamental importance have been learned by irradiating cells.

Origins of radiotherapy and radiobiology: separation of the influence of dose per fraction and overall treatment time on normal tissue damage by Reisner and Miescher in the 1930s.

The effect of fractionation on the response of normal tissues to irradiation was already investigated in the 1930s. Reisner (Reisner, A. Hauterythem und Röntgenstrahlung. Erg. Med. Strahlenforsch, 6: 1-60, 1933) measured the time course of skin erythema on thighs of humans by applying different doses per fraction while keeping constant total dose and overall treatment time. The results showed that acute skin damage was reduced with small doses per fraction. Two years later Miescher (Miescher, G. Tierexperimentelle Untersuchungen über den Einfluss der Fraktionierung auf den Späteffekt. Acta Radiol, 16: 25-38, 1935) published his results on late radiation effects in rabbit skin. He also reported that the main influencing factor for tissue tolerance was dose per fraction. In addition, he found indications that there was no impact of overall treatment time on the development of late reactions. Strandqvist in his famous monograph on the time factor in treatment of skin cancer (Strandqvist, M. Studien über die kumulative Wirkung der Röntgenstrahlen bei Fraktionierung. Erfahrungen aus dem Radiumhemmet an 280 Haut -und Lippenkarzinomen. Acta Radiol. (Suppl.) 55: 1-300, 1944), however, postulated that total dose and overall treatment time were the main determinants of local control as well as of normal tissue damage, apparently omitting to consider the findings of Reisner and Miescher in his own analysis. It is our impression that mainly due to the large influence of Strandqvist's work on radiobiological thinking the early findings on the normal tissue sparing effect of small fraction size have been forgotten and had to be rediscovered about 40 years later.