Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential

Round 1

Reviewer 1 Report

I have read the manuscript titled GENETIC POLYMORPHISM AND GENE THERAPY FOR 2 AGE-RELATED MACULAR DEGENERATION, STATE OF ART AND PERSPECTIVES by Stradiotto et. al. with great pleasure. This review article meets the requirements of IJMS standards. The authors summarize the progresses in discovery genetic polymorphisms associated with AMD and their potential role in risk assessment of response to therapy. Also, the authors proposed an overview of undergoing clinical trials to test therapeutic efficacy of new molecules linked to AMD genetics. The topic of the manuscript is important and will be interesting to retinologists.

I have some minor comments.

1)      Lines 34-38. Please insert information about a new consensus classification of neovascular AMD.

2)      Lines 98-100. Please insert to sentence the microRNAs. according to recent data, microRNA is a new epigenetic mechanism associated with AMD.

3)      Section Response to therapy. Please add recent data about association of CFI polymorphism with worse response to antiangiogenic therapy.

Author Response

Many thanks for your feedback and also for all your suggestions and comments performed with the aim to improve the quality of the paper. The corrections required have been performed as follows the response point by point:

1. we inserted a new consensus classification of AMD, particularly of the neovascular form;
2. we briefly indicated the miRNA mechanism of interference in gene expression;
3. we added literature about the association of CFI polymorphism and response to anti-VEGF treatment.

Reviewer 2 Report

Please see attachment.

Comments for author File: Comments.pdf

Author Response

Many thanks for your feedback and also for all your suggestions and comments performed with the aim to improve the quality of the paper. The corrections required have been performed as follows the response point by point:

1. we eliminated some references with lower scientific impact;
2. we added more references from more prestigious groups, particularly, but not exclusively, in the section of complement involvement description;
3. we gave more space to Zimura;
4. we named the Pharmaceutical companies involved in the development of complement-based AMD therapies;
5. we pointed out which are the most advanced molecules in the process of development;
6. we better explained the importance of gene therapy in the light of the current approval of a molecule in the treatment of retinal diseases.

Round 2

Reviewer 2 Report

None