It dealt with the study of the photodynamic effect, i.e., how the photonic energy of light is transmitted to tissues, such as the retina, through photosensitive pigments present in cones and rods, known by the name of rhodopsin and iodopsin, which, when activated by light, produce serious metabolic damage to the retina (photocoagulation). In fact, the body’s tissues and cells work thanks to oxidative phosphorylation and the metabolic energy produced by the Krebs cycle in particular in the mitochondria, the cytoplasmic particles rich in oxidative enzymes that I isolated by ultra-centrifugation. The energy is produced and conveyed to the body through a breathing process, with the consumption of oxygen and also through aerobic glycolysis processes. Since the retina connected to the brain by the optic nerve has been the focus of my attention for years, I was able to measure its energy production with the famous Warburg apparatus, conducting for years extremely complex experiments where tissues, cells and mitochondria placed in gauged containers and immersed in culture liquids, allowed measuring oxygen consumption and observing changes in cells and tissues. The peculiarity of the retina is that it is even able, unlike other tissues, to produce energy also in the absence of oxygen through anaerobic glycolysis, which is also typical of tumours. The retina is so precious to the body that it tries to survive even in extreme conditions in the absence of oxygen! That has always fascinated me. Another fascinating aspect of retinal tissue is its extraordinary photo-sensitivity to light due to the presence, as I mentioned above, of rhodopsin and iodopsin in the cones and rods. They are indeed two wonderful photodynamic and photosensitive substances. In this way, I understood how the body defends itself and it is with great emotion that I remember the experiments with calf retina isolated from the eyeballs and placed to breathe in the Warburg vessels.1,2
In those distant years, when everything had to be done “at home”, washing and sterilizing the glasswork and forming complex and delicate sterile culture solutions, the experiments required long preparation before inserting the retina and other tissues in the Warburg vessels. But the results were unforgettable for me. I used this complex methodology for many of the studies listed in the works published in prestigious scientific journals. The unexpected results were those observed on the isolated heart of a guinea pig, where the light radiation showed that the presence of bioactive substances that reacted to light, such as dihydroquinidine, even made it possible to reactivate cardiac contractions! Nature magazine published the results, but, as far as I know, no one has ever worked to get to the bottom of it. 3,4,5,6,7
Following my acute interest in the retina and realising that melatonin is produced by the pineal gland at night thanks to the close connections of the optic nerve with the hypothalamus and the brain, and reading a series of publications on the subject, Changxian Yi and I came to the conclusion that melatonin would probably have a rejuvenating action even on the retina. The clinical work, conducted in a famous ophthalmology centre in China with the utmost scientific rigour, provided indisputable evidence of the healing of retinal degeneration!
Pierpaoli W. and Santamaria L.
Ulteriori indagini sull’evidenza di processi fotodinamici naturali nella retina di vitello.
Atti della Società Italiana di Patologia, 7, 867, 1961.
Santamaria L. and Pierpaoli W.
Action of visible light and X-rays on isolated calf retina.
Communication at the 2nd International Congress of Radiation Research. Harrogate, England, 1962, p. 235 (abstract).
Pierpaoli W. and Pace G.
Modificazioni elettrocardiografiche da effetto fotodinamico su cuore isolato di mammifero.
Bollettino di Chimica Farmaceutica, 102, 20, 1963.
Pace G. and Pierpaoli W.
Photodynamic effect of dihydroquinidine on isolated hearts of mammals.
Nature, 199, 915, 1963.
Pace G. and Pierpaoli W.
Photodynamic effect of dihydroquinidine on the oxidative phosphorylation by mitochondria of mammal hearts.
Radiation Research, 25, 309, 1965.
Pierpaoli W., Pace G. and Grisler R.
Wirkung des Chinidins auf die oxydative Phosphorylierung und auf den K-Gehalt in den Mitochondrien des Herzmuskels.
Experientia, 21, 410, 1965.
Pace G., Pierpaoli W. and Clerici E.
Glicolisi aerobia di tessuti normali sospesi in differenti “media” di incubazione.
Atti della Società Italiana di Patologia, 9, 789, 1965.
Pierpaoli W.,Yi C.X. and Dall’Ara A.
Aging-postponing effects of circadian melatonin: experimental evidence, significance and possible mechanisms.
Int. J. Neurosci. 51, 339-340, 1990.
Pierpaoli W. and Regelson W.
The pineal control of aging. The effect of melatonin and pineal grafting on aging mice.
Proc. Natl. Acad. Sci. USA, 91, 787-791, 1994.
Yi C., Pan X., Ya, H., Guo M. and Pierpaoli W.
Effects of melatonin in age-related macula degeneration.
Annals of New York Academy of Sciences, 1057, 384-392, 2005.
NB: It is important to emphasize the fact that melatonin actions as reported in literature often depend on the chemical form and concentration used.