Solutions

Online Inquiry

* Your Name

Phone Number

* E-mail Address

* Services Interested

Project Description

Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Syndromic Microphthalmia

Syndromic microphthalmia is a complex developmental disorder resulting from syndromic microphthalmia development. Consisting of systemic microphthalmia (small eye) or even anophthalmia (absent eye), it is a rare disorder that is usually accompanied by other systemic abnormalities. Protheragen is one of the leaders in developing therapeutics for syndromic microphthalmia due to our full-service offering in molecular diagnostics, preclinical studies, and custom therapeutics.

Overview of Syndromic Microphthalmia

Syndromic microphthalmia describes an array of conditions which include abnormal development of the eye in addition to other systemic features. These splits are quite broad and portray the divergent genetic causes of the condition. Commonly associated anomalies are craniofacial, limb, and organ systems as well as intellectual disability. The genetic basis of syndromic microphthalmia has long been known, with several candidate genes having been recognized as critical for its pathogenesis. These genes such as SMOC1, STRA6, BMP4, and NAA10 are essential for the development of the embryo, especially for the eye and other organ systems.

Fig.1 Impact of the genetic variant in syndromic congenital microphthalmia canine model. (Murgiano L., et al., 2024)

Diagnostics Development for Syndromic Microphthalmia

Genetic Testing and Next-Generation Sequencing
For syndromic microphthalmia, causative mutations in a set of already defined disease-associated genes are usually identified through genetic testing. Next-generation sequencing (NGS) has transformed the field by allowing researchers to interrogate many genes at the same time, thus ensuring a higher yield of diagnosis. For instance, targeted NGS panels that capture the SMOC1, STRA6, BMP4, and NAA10 genes have been designed for microphthalmia.

Whole-Exome Sequencing and Whole-Genome Sequencing
With regards to the absence of a causal mutation from the comprehensive targeted NGS panel, WES or WGS sequencing may be used. WES targets the coding portion of the genome, whereas WGS encompasses the complete genome.As for new findings, there have been recently reported WES studies that have uncovered novel mutations in a NAA10 gene which add to the known genetic diversity of syndromic microphthalmia.

Therapeutics Development for Syndromic Microphthalmia

Recent attempts at drug therapy development for syndromic microphthalmia have been met with challenges owing to the genetic and phenotypic variance characterizing the condition. Nonetheless, breakthroughs in molecular biological understanding of the eye developmental processes provide tools for more precise drug design. For instance, there is ongoing research on small molecule inhibitors of the BMP signaling pathway that is known to be perturbed in some types of syndromic microphthalmia. Furthermore, given the pivotal role of the STRA6 gene in retinol (vitamin A) transport, drugs which augment retinol metabolism might be of therapeutic benefit for certain microphthalmia syndromes.

Our Services

Protheragen is focused on moving forward with the research and development of therapies for syndromic microphthalmia. We integrate diagnostic molecular, preclinical research, and therapeutic development. By leveraging cutting-edge technologies and a multidisciplinary approach, Protheragen aims to provide innovative solutions for this complex and challenging condition.

Genetic Target Identification & Pathway Validation Services

Protheragen supports clients in mapping and validating novel and established genetic drivers of syndromic microphthalmia using next‑generation sequencing (NGS), bioinformatic pathway analysis, and functional genomics. We perform targeted gene panel sequencing, whole‑exome sequencing (WES), and copy‑number variation (CNV) analysis to identify pathogenic variants in patient‑derived genomic data, then prioritize candidate genes using functional enrichment, protein–protein interaction (PPI) networks, and evolutionary conservation scoring.

We conduct CRISPR‑Cas9‑mediated gene knockout, knock‑in, and overexpression in human pluripotent stem cells (hPSCs) and ocular progenitor cells to validate gene function during ocular development. Assays include quantitative PCR (qPCR), Western blotting, immunofluorescence, and RNA sequencing (RNA‑seq) to measure changes in gene expression, protein localization, and pathway activity. For pathway analysis, we focus on retinoic acid signaling, SHH, WNT, BMP, and Notch cascades—all centrally dysregulated in syndromic microphthalmia—to define actionable therapeutic nodes. Protheragen also provides variant pathogenicity classification using ACMG/AMP standards and computational modeling to predict mutation impacts on protein structure and function.

3D Ocular Disease Model Development Services

We specialize in generating physiologically accurate, patient‑relevant preclinical models for syndromic microphthalmia without animal or clinical field work. Our core offerings include:

Patient‑derived iPSC‑optic vesicle models: Reprogramming patient fibroblasts or peripheral blood mononuclear cells (PBMCs) into induced pluripotent stem cells (iPSCs), then differentiating them into 3D optic vesicles that recapitulate key disease phenotypes including reduced size, impaired proliferation, increased apoptosis, and disrupted laminar organization.
Gene‑edited hPSC ocular models: CRISPR‑engineered isogenic control and mutant cell lines carrying STRA6, ALDH1A3, SOX2, PAX6, or other disease‑causing variants to enable controlled phenotypic and therapeutic screening.
Retinal organoid systems: 3D retinal organoids that model retinal neurogenesis, photoreceptor development, and retinal pigment epithelium (RPE) maturation, with structural and molecular readouts relevant to syndromic microphthalmia.

High‑Throughput Screening (HTS) & Therapeutic Candidate Evaluation Services

Protheragen operates a dedicated high‑throughput screening platform tailored to syndromic microphthalmia, supporting the discovery and optimization of small molecules, gene therapy vectors, peptide therapeutics, and RNA‑based modulators. We design custom phenotypic screening assays using optic vesicle and retinal organoid models, with endpoints including:

Optic vesicle size restoration and morphological rescue
Retinal progenitor cell proliferation and survival
Expression normalization of dysregulated developmental genes
Apoptosis reduction and caspase inhibition
Recovery of retinal lamination and cell‑type specification

We offer targeted small‑molecule libraries focused on developmental pathways, nuclear receptors, kinase inhibitors, and anti‑apoptotic compounds, alongside custom compound screening for client‑provided molecules. Following primary screening, we perform dose–response validation, counter‑screening, and selectivity profiling to eliminate false positives and prioritize lead candidates. Protheragen also provides structure–activity relationship (SAR) analysis and in vitro pharmacokinetic (PK) profiling to support lead optimization.

Mechanism‑of‑Action (MoA) & Translational Biomarker Services

To clarify therapeutic activity and enable clinical translation, Protheragen delivers comprehensive mechanism‑of‑action studies and biomarker discovery for syndromic microphthalmia therapies. Using transcriptomics, proteomics, phosphoproteomics, and single‑cell RNA sequencing (scRNA‑seq), we map compound‑induced changes in gene expression, signaling pathway activity, and cellular state within ocular models. We identify downstream effectors, transcription factors, and secreted factors that mediate phenotypic rescue, supporting rational therapeutic design.

In parallel, we develop quantitative biomarker assays for monitoring therapeutic response, including:
Gene expression biomarkers (qPCR, digital PCR panels)
Protein biomarkers (ELISA, multiplex immunoassays)
Morphometric biomarkers (automated image analysis of optic vesicle/organoid size and structure)
Cell fate and differentiation biomarkers (flow cytometry, immunofluorescence quantification)

Custom Assay Development & Validation Services

Protheragen designs and validates bespoke functional assays aligned with client project goals and disease mechanisms. These include:

Ocular progenitor cell proliferation and viability assays
Optic vesicle morphogenesis and growth assays
Retinal differentiation and lamination assays
Signaling pathway reporter assays (retinoic acid, WNT, SHH, BMP)
Gene correction and genome editing efficacy assays for gene therapy
Apoptosis, oxidative stress, and ER stress assays in ocular models

All assays are validated for precision, accuracy, linearity, and reproducibility, with standardized operating procedures (SOPs) and regulatory‑ready data output. Clients receive fully validated assay protocols, validation reports, and assay transfer support to enable in‑house implementation.

Diagnostics Development

Therapeutic Development

Disease Models

Bmp4 Knockout Mouse Models
Naa10 Knockout Mouse Models
Strabismus (strab) Zebrafish Models
Smoc1 Knockout Mouse Models
Induced Pluripotent Stem Cells (iPSCs)

Protheragen's preclinical research services are designed to support the development of novel therapies for syndromic microphthalmia. Our team of experts utilizes advanced animal models and in vitro systems to study the molecular mechanisms underlying the condition and to evaluate the efficacy of potential therapeutic agents. If you are interested in our services, please feel free to contact us.

Reference

Murgiano, Leonardo, et al. "A naturally occurring canine model of syndromic congenital microphthalmia." G3 Genes| Genomes| Genetics 14.6 (2024).

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.