Nanoparticle-Based Retinal Prostheses: The Effect of Shape and Size on Neuronal Coupling

Round 1

Reviewer 1 Report

This paper provides a theoretical analysis of how photocurrent in the P3HT nanoparticles is produced for photovoltaic neural stimulation. Especially the effect of nanoparticles' shape is rigorously investigated. I have several comments that could improve the manuscript.  

 

1. Is there any supporting references regarding the physical dimension the particle authors modeled? I was wondering whether the shape and size of NPs can be actually synthesized and used to stimulate the neuron cell.

 

2. On page 6 line 142, the authors have mentioned that electric potential exhibits oscillation. Do authors mean the temporal electric potential oscillation? or spatial?

 

 

3. Is the voltage range of -0.06 mV~0.06mV sufficient to trigger an electrochemical reaction producing O2-?

 

4. In table 1, authors have mentioned the current produced at the NPs. Is this sufficient current density(A/cm^2) or charge (C) to elicit an action potential? 

 

5. There is weak bound between photocurrent generation to neural stimulation. Authors should add some detailed explanation or simulation related to it.

 

6. What happens when particles aggregate?

Author Response

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Reviewer 2 Report

The article is about the development of artificial vision using nano particles. Such nano particles could  be easier implanted than other retinal implants that have been already on the market. Therefore, the article is scientifically relevant.

 

The abstract says that the nano particles can we injected without a surgical treatment. It is not described how the particles are placed in the retina. The referred paper describes the injection into the subretinal space with typically involves a vitrectomy which is definitely a surgical procedure. I would recommend to change the wording to … minimal invasive … which probably describes the procedure more adequate.

The introduction only refers to two papers regarding other retinal prostheses. I recommend to introduce newer literature.

 

The modelling of such devices is complex and errors can easily happen.  The authors should describe how the correctness of the method was verified e.g. by applying the method to well-known geometries or by comparing it to experimental data.

 

In line 55 it is written that the surrounding has a relative permeability of 6. Literature or experimental data should be referred to this value.

 

It has been written that the role of ion electrodiffusion and of ionic screening has been neglected in the current model. The reader needs to know why ion electro-diffusion and ionic screening was not taken into account. There need to be at least an estimation of error using the current model so that the reader can understand the relevance of the results.

 

In the results section it has been written that the calculations have been made for a light source of 1 W/m2. Please explain the relevance of this value by describing which light condition in human environment this would represent.

 

Table 1 describes the superoxide current. Please describe why the superoxide current is relevant and if there are other currents that may be of interest.

 

A table that summarizes the voltage results for all modeled geometries would be useful.

 

The relevance of the voltage values is not clearly discussed. The numbers are much lower than the necessary cell membrane changes in the retina. The reader needs to get an understanding why the authors think these numbers are relevant and sufficient for retinal stimulation. If the authors believe the voltage of several NPs in series will be summed up, then this should be explained. In this context it needs to be discussed if several small NPs would still be less preferable than a low number of large NPs.

 

 

The elliptic NPs seems to have advantages. However it is not clear how they can get maintained in a certain direction. The injection of NP would probably in a random order of orientation. Please explain why this is relevant.

 

The discussion does not refer to any literature. The discussion should display the results in regards to the current knowledge. Literature should be used to support the correctness of the results.

 

The discussion mentions that the interface between neurons and NPs may be worse with larger NPs. This need to be explained.

 

There are a few spelling mistakes like “secondary” instead of “secondary”

Author Response

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Reviewer 3 Report

This is a good manuscript studying and discussing the electrostatic polarization of the nanoparticles which is potentially be used as the retinal prostheses. The author builds a beautiful physical model with light incident to the NPs to study the effect of the NPs radius and the shape. A clear conclusion is that the radius increasing causes the stronger signal but adding other difficulties in the neuron interacting. The ellipticity and the orientation also matters. But the author didn’t give any more information of how to overcome these issues. One more issue is that the author mentioned the photoreceptor, retinal prostheses in the introduction, but then slightly moved to the mathematical discussion and didn’t come back to give clear picture of the NPs working in the eye. Overall, I suggest to publish this manuscript if the author could modify the manuscript as I mentioned. 

Author Response

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Reviewer 4 Report

Photoreceptor death is a leading cause of blindness worldwide, secundary to the development of retinal and macular pathologies, such as Retinitis Pigmentosa or Maculopathy. Despite it affects several millions of people per year, pharmacological and surgical treatments, such as intravitreal injections or photodynamic laser treatments, do not always provide a resolutive cure.

The use of nanoparticles as retinal prosthesis introduced several advantages that the authors describe in the article. In order to assess the effect of distribution of nanoparticle shape and size, they simulated various scenarios of light-induced nanoparticle electric potential as a function of radius and ellipticity of the NP.

I think this is an interesting paper and deserves to be published if minor changes are considered:

 

They talk about pharmacological treatments. It would be interesting if they mention in the introduction about other possible  treatment such as light and the therapeutic effects of some wavelengths of light (see for example article [1])

1.         Menéndez-Velázquez, A.; Núñez-Álvarez, C.; Olmo-Aguado, S. del; Merayo-Lloves, J.; Fernández-Vega, A.; Osborne, N.N. Potential Application of Photoluminescent Filters for Use in Ophthalmology. Optical Materials 2018, 86, 505–511, doi:10.1016/j.optmat.2018.07.065.

Author Response

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Round 2

Reviewer 1 Report

The authors modified their manuscript based on the comments. 

Author Response

Thanks a lot for your previous valuable contributions to our manuscript.

Reviewer 2 Report

The manuscript has been significantly improved.

Literature has been added but it would be good if latest literature about "clinical" results from Zrenner et al. and Palanker et al. would be added. This is relevant to understand the need of improvement and further development and would improve the quality of the paper.

Author Response

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