June 2017
Volume 58, Issue 8
ARVO Annual Meeting Abstract  |   June 2017
Multi-Characteristics Opsin and Nano-enhanced optical delivery enable vision restoration
Author Affiliations & Notes
  • Samarendra Mohanty
    Nanoscope Technologies, LLC, Arlington, Texas, United States
  • Sanjay Pradhan
    Nanoscope Technologies, LLC, Arlington, Texas, United States
  • Sivakumar Gajjeraman
    Nanoscope Technologies, LLC, Arlington, Texas, United States
  • Sulagna Bhattacharya
    Nanoscope Technologies, LLC, Arlington, Texas, United States
  • Weldon Wright
    Nanoscope Technologies, LLC, Arlington, Texas, United States
  • Footnotes
    Commercial Relationships   Samarendra Mohanty, Nanoscope Technologies, LLC (E); Sanjay Pradhan, Nanoscope Technologies, LLC (E); Sivakumar Gajjeraman, Nanoscope Technologies, LLC (E); Sulagna Bhattacharya, Nanoscope Technologies, LLC (E); Weldon Wright, Nanoscope Technologies, LLC (E)
  • Footnotes
    Support  NIH Grant EY026483, NIH Grant EY025717, NIH Grant EY025905
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4083. doi:
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      Samarendra Mohanty, Sanjay Pradhan, Sivakumar Gajjeraman, Sulagna Bhattacharya, Weldon Wright; Multi-Characteristics Opsin and Nano-enhanced optical delivery enable vision restoration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4083.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Photodegenerative retinal diseases lead to loss of vision in millions of individuals. Currently, no surgical or medical treatment is available though optogenetic therapies are in clinical development. While optogenetic stimulation have advantages of cellular specificity and minimal-invasiveness as compared to electrode array, clinical translation suffers from two major drawbacks: (i) requirement of active illumination since conventional opsin requires high intensity of light for stimulation, and (ii) lack of approach for delivery into spatially-targeted regions of degenerated-retina. We hypothesized that vision enhancement at ambient light level can be achieved using highly photosensitive Multi-Characteristics Opsin (MCO) by viral or optical delivery.

Methods : Synthetic genes encoding for MCOs (I & II) were synthesized and cloned into plasmids having specific promoter and reporter. The bipolar cells were transfected with MCO using AAV or Nano-enhanced Optical delivery (NOD). The expression of MCOs in cell membrane was quantified using confocal microscopy. To determine the light dependent photocurrent, the MCO-expressing cells were exposed to light at ambient levels. Measurement of intensity thresholds using the visual water maze task was conducted at different time points after intravitreal injection of different doses of MCO to rd10 mice. Further, biodistribution and toxicity studies were carried out using qPCR, and immunohistrochemistry. For NOD, after intravitreal injection of Gold nanorods and MCO-plasmids, a NIR laser beam was directed to the retina.

Results : MCO genes are reliably delivered to specific retinal cells via intravitreal injection of AAV carrying MCO or via NOD. Using NOD, we show that MCO-plasmids could be delivered to retina in-vivo with continuous wave laser with exposure of few seconds. Significant improvement in visually guided behavior observed in mice having MCO-expression in retina. Notably, the improvement in visually guided behavior was observed even at light intensity levels orders of magnitude lower than that required for ChR2. Biodistribution study using qPCR analysis showed negligible quantities of MCO-gene in different non-targeted organs.

Conclusions : Safe virus-mediated MCO-delivery has potential for effective gene therapy of advanced stages of retinal degenerations in patients. NOD will lead to new clinical approach for treating patients with geographic atrophies.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.


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