John R. Trevithick, PhD, A Canadian Vision Research Pioneer Leaves Us at Age 82.

It is my sad task to note the passing of John Trevithick, PhD, at age 82, at his home in London Ontario. (2/20/2018)

John is well known to many ARVO (Association for Research in Vision and Ophthalmology) and ISER (International Society for Eye Research) members, since the early 70’s as one of the first researchers who took up the lens as a model for cell differentiation. A pioneer in the explorations of cAMP in N. Crassa, he sought to explore this signaling molecule in mammalian cell differentiation. The lens epithelial to fiber cell transition continues during the entire life of the mammalian lens.

            Along the way John explored cataract mechanisms of course but as a biochemist he always was interested in the fundamental knowledge of cell physiology and biochemistry that could be revealed. His lab was one of the first groups to optimize culture media conditions to permit the study of whole living lenses in tissue culture. This permitted the precise manipulation of external and internal chemistry and was used to correlate research done with diabetic rat models and the RCS model. Interesting effects on the RCS lens posterior opacity caught his attention in this model, where degeneration was occurring in the retina. Along with diabetic cataract models his group explored the contribution of antioxidant biochemistry to degenerative processes in the lens and retina. Some surprising findings, of dramatically slowing cataract formation and other degenerations by supplementing endogenous antioxidants resulted in a couple Nature publications. I joined his lab in 1988 as a PhD student, at the University of Western Ontario.

            John took me, and other students, to many meetings around the world and he spent a lot of care teaching us to repeat work and make sure we published reproducible data. He let us write papers early and we tended to graduate with a few publications already completed. With John, I enjoyed discovering that the diabetic rat lens was iso-osmolar for several weeks by dumping Taurine and free amino acids to perfectly balance the increase in sorbitol. Then this amino acid deficiency led to the loss of GSH, ATP production, ion transport capacity, and finally the loss of fluid regulation. This was a lesson John taught many of us, that if you delve into the biochemistry of even an old model system, you will likely find some new knowledge. Do not assume that a decade of literature on a topic has documented everything important.

            John was Emeritus professor of Biochemistry and had continued also as a professor in Kinesiology, working to explore the effects of exercise on the eye in normal and diabetic rats, working with Tom Dzialoszynski and Earl Nobel. Most recently they spent the last several years on space radiation effects upon the lens. That work, funded by the Canadian Space Agency, involves trips to UBC and the use of their busy cyclotron facility. John, always curious to the very end and finding ways to fund vision research in Canada, which does not have a vision-focused funding category as we have in the USA.

If any members of the vision research community have a memory of John Trevithick they would like to share, please email to me at 

Mitton@oakland.edu

Tom and I are planning to write a short memorial paper about John and his contributions to vision science in Canada and internationally. Many of us owe our thanks to John for the time he devoted to ARVO, ISER, vision science and teaching the next generation of scientists.

A mostly complete list of John Trevithick’s publications in PubMed are found here:

John Trevithick Papers in PubMed

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Our Lab’s latest publication: Norrin treatment testing for survival of optic nerve cells.

Norrin treatment improves ganglion cell survival in an oxygen-induced retinopathy model of retinal ischemia.  In Experimental Eye Research (2017), accepted, in press.

RGCellLivingEye

 

Highlights
• Norrin treatment accelerates recovery of the mouse OIR model from ischemic insult.
• SD-OCT can compare NFL/GCL (nerve fiber layer/ganglion cell layer) thickness in vivo.
• Norrin treatment counters thinning of the NFL/GCL in the mouse OIR model.
• Norrin treatment increases the surviving population density of RGCs in OIR retinas.

This paper is one of the first to use the in vivo imaging methods of intrinsic fluorescence with a transgenic mouse strain to see individual ganglion cells in the living mouse eye, and to even follow their morphology over a period of many days in the mouse model of oxygen-induced retinopathy. This was done with a Phoenix Research Labs‘ system, in this case the Micron-III version of their imaging system. We used a light filter set recommended by Phoenix to image yellow-fluorescent protein (YFP). Axons and dentrites could be seen on single cells in anesthetized mice. Amazing!

We also employed SD-OCT (Spectral Domain – Optical Coherence Tomography) to capture 3D structural records of the mouse retina and then to measure the changes in thickness of the very thin Nerve Fiber Layer / Ganglion Cell Layer (NFL/GCL).

The ability to use these imaging systems in vivo, which are also used in clinical analysis of the Human retina, enables us to see disease processes as they progress and to use far fewer mice to get the answers to research questions. In this case we were testing the ability of Norrin (Norrie’s Disease Protein) to be used to help avascular regions of retina recover their vasculature more quickly and improve the survival of RGCs (retinal ganglion cells) from the stress of low oxygen. RGCs are the cells that form our optic nerves. Millions of RGCs per eye have axons that extend all the way into connections with our brain. This bundle of a million “wires”, or axons, is the optic nerve.

Our research here and that of other laboratories suggest that Norrin and other agents might have use to maintain a better vasculature in diseases where the blood vessels and capillaries are damaged, such as ROP, Diabetic Retinopathy and AMD.

kpmitton wants to share Happy Mole Day 10/23 from 6:02am to 6:02pm

#6.022×10^23 #happyMoleday chemists, biochemists, physicists, science students https://t.co/8EuaUgzsoH Oct 23 #1023 @oaklandu @AndrewLocal4

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The Science Rant: Cherry Picking and Bad Pharma: how Patients and Doctors are fooled by incomplete information on prescription drugs.

Bad Science is really not doing science right at all. If you cut corners or do not repeat an experiment to make sure it is reproducible, you can end up with egg on your face as a scientist. At best the target for teasing by your colleagues, or at worst, a person that is never trusted again in the science world.

Bad science may also occur when money is part of the motivation equation in the form of “for profit”. Unfortunately, that is the context where commercial Pharma research occurs, including their clinical trials. With shareholders to pay, there is a strong executive pressure to get the product developed and flying out of the pharmacy on Doctor’s prescription pads.

For all of us as Patients, this can have bad consequences. For our Doctors, they may be making prescription decisions based on information that is skewed or incomplete. They can be in a position where they cannot even get the full story on many of the drugs they must choose from. The Pharmacist will be in the same position as your Doctor. The problem that is keeping all three of us in the dark is reporting bias on the part of the drug developer. That is, under reporting of negative trial results, and basic cherry picking of trial results.

Read more about these problems in my blog post at TheScienceRant.com

If you are a medical student or practicing doctor now, how do you know the drugs you are prescribing actually work? Turns out you might often not have the full truth about all clinical trials pertaining to the drug in question. I recommend you read more here:

http://thesciencerant.blogspot.com/2013/07/cherry-picking-and-bad-pharma-how.html?m=1

Solar Cell #3668 Flying around the Globe.

This is the location of solar cell number 3668 on the Solar Impulse 2 aircraft. This special plane is currently flying around the world. Solar cell number 3668 is the solar cell that I have sponsored on behalf of the Eye Research Institute of Oakland University. Funds derived from sponsors of solar cells on this aircraft are used by the Solar Impulse Foundation to develop educational materials for use around the globe. While I am a vision scientist, gene expression researcher and biochemist, I am also a science and research educator. A Professor here at Oakland University in Rochester and Auburn Hills, Michigan.

I spent much time poking around the map of available photovoltaic cells, choosing just the correct one for sponsorship. I settled on 3 6 6 8. The numbers have meanings to us here in the Eye Research Institute.

Three 3 is the number of different cone opsin genes and thus cone photoreceptors in Humans and other species that are trichromats. We can differentiate colours using three overlapping color sensitive windows for short, medium and long wavelengths of light. Call them blue, green and red for simplicity.

Six 6 is the number of different major types of retinal neurons that provide us with light detection and vision. They are rod cells, cone cells, bipolar cells, amacrine cells, horizontal cells, and ganglion cells. I also like 6 because  “building 6” housed most of the National Eye Institute’s intramural labs at the NIH in Bethesda MD, when I was a post-doctoral fellow there in 1995 to 1997.

Sixty Eight 68: the year that the founder of our Eye Research Institute, and first Director, V. Everett Kinsey PhD, began eye research here at Oakland University. Dr Kinsey shared the Lasker medical prize in 1956 with Dr Arnall Patz MD, for designing and managing the research to demonstrate that oxygen was an important driving factor in affecting the severity of retinopathy of prematurity in premature infant eyes. This turns out to have been one of the first pioneering examples of a very important concept in human medical research used today: the multicenter clinical trial.

Dr Kinsey is also known at the father of the NEI, as the person who proposed and then convinced other vision scientists, clinicians and the US Congress that the NIH should also have a National Eye Institute. Dr Kinsey then chaired the first national advisory panel of the NEI and chaired the committee that selected the NEI’s first Director, Dr Kupfer. The NEI also got started in 1968.

Finally, I have spent much of my own research career studying how genes are regulated and expressed to give different cells their different identities and functions in the body. One favorite model was the Rhodopsin gene itself, the gene encoding the protein that captures a single photon of light using bound cis-retinal and thus converts the energy of light into a neural network signal that is transmitting to our brains, one of the most important senses available to a sighted person. Our retinas recycle cis-retinal and it is used many times, in a sustainable fashion, which mirrors the concept of renewable energy demonstrated so well by the Solar Impulse 2 team flying around the globe now, using only the power of the Sun.

You can learn more about Solar Impulse 2 at :

http://www.solarimpulse.com/join-us