C5. Synergistic Progress of the BRP
The BRP has been far more productive and efficient than the funding of an individual R01 for each of the same investigators for
at least three reasons, discussed in greater detail below: 1) The collaborative nature of the BRP has accelerated the development
of AOSLO technology within the BRP. 2) The BRP has increased the dissemination of AOSLO technology to researchers outside the BRP.
3) The BRP has helped to create a commercialization path for AOSLO technology in ophthalmology and vision research.
C5.1. Accelerated AOSLO development within the BRP
The BRP has accelerated the development of adaptive optics technology because each site has benefitted from the aggregate wisdom of
all six partnering institutions. Without the BRP, development would have occurred mostly independently with substantial redundancy of
effort as different groups competed for similar scientific and engineering goals. The BRP allowed six different laboratories to
distribute the engineering effort as well the scientific projects in a much more efficient and coordinated manner. A small subset of
the many examples of cooperative sharing within the BRP is listed below.
- Individual modules (eg. AO control system, user interface, scanning optics, light detectors) of the 2nd generation
instruments were designed by committees with representation from multiple BRP sites
- AO control loop software from several sites was shared
- The group determined the maximum permissible light exposures for safe use of AOSLOs at all sites
- LLNL, an engineering group, successfully constructed and deployed an AOSLO at DEI, a clinical research group and
trained them to operate it
- Extensive sharing of software from UCB and other groups for image registration and control of eye movement
artifacts
- Extensive sharing of experience with MEMS mirrors and drivers among all groups
- IU shared a method to avoid backscatter from the deformable mirror surface with other groups
- PI organized a review team consisting of BRP partners IU, UR, and UCB-AR that visited LLNL to troubleshoot their
instrument
In the past, the Center for Adaptive Optics, funded by the National Science Foundation, has also provided a forum to encourage
collaboration among members of this BRP as well as a second BRP devoted to AOOCT. However, funding for the Center ends in 10/31/09
at which point BRP funding will provide the only multi-institutional support coordinating and accelerating the efforts of individual
laboratories.
C5.2. Dissemination of AOSLO Technology Outside the BRP
The BRP is committed to broadly sharing its technology and scientific findings. The mechanisms for disseminating information,
beyond the usual mechanisms of publication and presentation at scientific meetings, include the following:
Trainees: The BRP encourages graduate students and postdoctoral fellows to immerse themselves in the spectrum
of disciplines represented in the partnership. The BRP has committed travel funds for trainees to attend BRP meetings and to visit
other sites, especially for clinical trainees to visit engineering sites and vice versa.
BRP Website: The University of Rochester's Center for Visual Science maintains a website that describes the
activities and latest results of the BRP. http://www.cvs.rochester.edu/brp/
C5.2.1. Collaborations with Academic Institutions Outside the BRP
- Four investigators in the Department of Ophthalmology at the University of Pennsylvania, Jean Bennett, Eric Pierce, Ed Pugh, and
Dwight Stambolian have asked UR to build them an AOSLO for research projects involving imaging receptors and RPE in Leber's congenital
amaurosis and AMD
- Artur Cidecyian and Sam Jacobson plan on using the UR AOSLO for research on patients with inherited retinal degenerations
- Ed Stone, University of Iowa, is collaborating with UR in imaging patients with retinal degenerations
- Steve Russell, University of Iowa, is collaborating with UR on the role of the radial peripapillary capillaries in glaucoma
- Robert Massof, Willmer Eye Institute, is planning to the development of an AOSLO for improving the models of the progression of
retinitis pigmentosa, in consultation with the BRP
- Joe Carroll, Jay Neitz, and Maureen Neitz of the Medical College of Wisconsin are using AO control software developed by UR in
studies of the retinal mosaics of color deficient human eyes in which the genetic cause of the deficiency has been characterized
- Jason Porter and Heidi Hofer are each building AO retinal cameras at the University of Houston and will rely on the BRP for
technical support
- Rigmor Barass at Buskerud University College, Norway is looking to the BRP for technical support for her adaptive optics system
for imaging the retinas of color-deficient eyes
- Richard Libby, a new investigator at the University of Rochester, will collaborate with Williams' group on imaging ganglion cells
in a mouse model glaucoma
- The BRP has agreed to provide information about AOSLO technology, in particular stabilization against eye movements in high resolution
imaging, to Melanie Campbell at Waterloo University
- The IU group has developed its own software package for AO control which has been placed on a CVS server for public access. Groups
that have downloaded the software include The University of Illinois (Dr. Shahidi), The University of California, San Diego (Dr. MacLeod),
Queensland University (Dr Atchison), Massachusetts General Hospital (Dr. Lin) and Boston University (Dr. Bifano)
- The dual deformable mirror system developed by LLNL has been shared with a BRP focused on retinal imaging systems that combine OCT and
AO (Jack Werner, PI).
- IU has provided advice on approaches for Physical Science's adaptive optics program with the Air Force Research Laboratories
- UR and UCB-JF are collaborating with Dennis Dacey, U Washington on fluorescence imaging of primate ganglion cells with rhodamine
dextran
- Nanotechnology grant – 12 investigators developing light-activated ion channels and light-switched molecules (e.g. "caged"
anti-VEGF)(UCB-JF)
- Roorda has established a collaboration with Jacque Duncan, an ophthalmologist investigating retinal disease at UCSF and a new AOSLO
instrument will be deployed in their department
- Rich Kramer: synthetic photoisomerizable azobenzene-regulated K+ (SPARK) channels (UCB-JF)
- The Flannery lab is continuing to collaborate with Lu Chen at UC Berkeley on the development of improved fluorescence sensors of
synaptic activity in neurons - the first generation of these sensors is Synapcam a calmodulin [Ca++] fluorescence sensor of synaptic
activity in neurons (UCB-JF). We aredeveloping new postsynaptic and presynaptic sensors of neuronal activity
- The Flannery lab is collaborating with Richard Weleber and Peter Francis or the University of Oregon Ophthalmology, Martha
Neuringer of the Oregon Primate Center and Bill Hauswirth of U. Florida in a toxicity study of AAV vectors in the primate retina for
treatment of Usher syndrome which will employ AO fundus imaging to assess retinal toxicity from subretinal injection of AAVvector.
(UCB-JF)
C5.2.2. Collaborations with Industry and Commercialization
- The BRP is translating AOSLO technology to Optos, Inc. who plan to incorporate a high resolution imaging capability into their
wide field retinal camera
- Bausch and Lomb, Inc. is supporting two research contracts with UR to explore the utility of AOSLO imaging in the development of
pharmacological interventions for AMD and glaucoma
- Merck is also interested in working with BRP sites to explore the utility of AOSLO in studying the effects of pharmacological
interventions for AMD and glaucoma
- A number of companies that make deformable mirrors are collaborating with the BRP on the development of improved mirrors for
vision science. These include Boston Micromachines, Aoptix, Iris, AO, Umachines, and Imagine Eyes
- Neurotech will collaborate with Roorda's group at UCB and UCSF as well as DEI
- Second Sight and DEI are collaborating on imaging their retinal prosthetics in vivo with AOSLO technology
- Pfizer Ophthalmology and UCB-JF are collaborating on clinical testing of anti VEGF small molecules
- Ceregene and UCB-JF are collaborating on clinical efficacy testing of AAV neurturin and AAV Nt4/5 photoreceptor neuroprotection
therapy for RP and "dry" AMD
- IU has had discussions of the future of adaptive optics imaging with Topcon, and also had a site visit and demonstrations with
them
C5.3. The BRP Strategy for Commercialization Involves
- Demonstrating the clinical value of AOSLO technology with projects directly funded by the BRP
- Collaborating with other clinical researchers in ophthalmology to provide them with access to AO technology which accelerates
the development of new applications for the technology
- Collaborating with corporate partners to generate interest in AOSLO Technology. For example, Bausch and Lomb, along with a
number of other companies invested in ophthalmic instrumentation, have expressed an interest is in using the device to study the
efficacy of drug delivery systems for human retina
- Licensing. The University of Rochester and the University of Houston have bundled their joint intellectual
property relevant to AOSLO technology and have licensed this suite of patents to Optos, Inc. Optos plans to develop an fundus
camera that is AO-equipped.
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