Welcome to the video on retinoblastoma.
In this video, we will be discussing what retinoblastoma is,
the diagnosis criteria,
the underlying genetic cause,
the mechanism of disorder, and treatment options currently available.
But before we begin, we would like to note that
This video content is intended for informational and educational purposes only
and does not provide a diagnosis. Individuals who experience similar signs and symptoms
are advised to seek professional help.
So let's get started.
What is retinoblastoma?
Retinoblastoma is a rare type of eye cancer
that occurs most often in children under the age of 5.
It accounts for approximately
2% of all cancers that occur in children aged 0-14 years of age.
Retinoblastoma begins in the part of the eye known as the retina. The retina
is a thin layer of tissue that lines the back of
the eye and is made up of nerve tissues,
which sense light
and send signals through the optic nerve
to the brain to be interpreted as images, thus
enabling vision. This cancer
can affect either one eye
known as unilateral retinoblastoma, or it can affect
both eyes, known as bilateral retinoblastoma.
The initial detection of retinoblastoma usually begins when parents realize
there's something wrong with their child's eyes. Some common signs that
parents may notice are leukocoria,
which is a white glare in the pupil,
strabismus, which is eyes looking in different directions,
Heterochromia,
which is different colored irises,
eye redness, eye swelling and inflammation,
blurred vision,
and squinting,
and even pain in the eyes.
When it comes to diagnosing retinoblastoma,
it is important to note that retinoblastoma can be divided
into two categories.
The first being intraocular retinoblastoma and the second being extraocular
retinoblastoma.
Intraocular retinoblastoma can be divided into five groups - groups A to E based
on how likely the eye can be saved and refers
to cancer being contained within the eye.
On the other hand,
extraocular retinoblastoma is divided into four stages - stages 1 through 4
based on the spread of the cancer
and refers to the cancer spreading outside of the eye
to distant parts of the body.
Some tests and procedures commonly used to diagnose
retinoblastoma include eye exams, ultrasounds, and magnetic resonance imaging.
These procedures are conducted by opthalmologists, also known as eye specialists.
An eye exam is where the specialist
checks eye health
And also looks for signs of retinoblastoma, some of which
include glaucoma,
which is increased eye pressure,
proptosis, which is enlarged eyeball,
and they also explore other eye conditions such as
lazy eye. The specialist may
also take images of the inside of the eye
to determine the shape, size, and location of the tumours.
Another procedure includes an eye ultrasound.
This method is used to find a location of the
tumour in the eye. It is conducted with a wand-like
structure that uses sound waves to take images inside the eye.
Lastly, an MRI can also be used.
MRI uses radiofrequency waves to determine the size
and number of tumours in the eye.
This technique is used to investigate the severity of the
spread of cancer from the eye to other parts of the body.
So,
you may be wondering by now
what the underlying genetic cause of
retinoblastoma
is and how it is inherited.
So,
let's get to that right now.
Retinoblastoma arises due to mutations in the retinoblastoma gene
commonly abbreviated as
RB1 gene
This gene is located on chromosome 13,
and codes for a protein called the retinoblastoma protein.
This protein
plays an important role in controlling the division of cells within the body.
Retinoblastoma can be either heritable or non heritable.
In heritable retinoblastoma,
The mutated RB1 gene
is inherited from either one parent and the mutation
is found in all cells of the body. More specifically,
in each cell
there is one mutated RB1
allele and one normal RB1 allele. Affected individuals
could possibly pass the mutation down to offspring via an autosomal dominant mode
of transmission. Despite this inheritance pattern, the patient
usually develop the second mutation in the normal allele as well
as this is necessary
for the development of retinoblastoma. This phenomenon is known as
Knudson's two-hit hypothesis,
which states that both mutated alleles of a gene are
necessary for the development of cancers,
like retinoblastoma.
On the other hand,
in non heritable,
retinoblastoma,
the individual does not inherit the mutated RB1 gene but
rather than mutations in both alleles of the RB1 gene
are acquired over time and most often acquired
before the age of one.
There's some key differences between heritable
and non-heritable retinoblastoma. For example, the symptoms experienced by those with heritable retinoblastoma patients
are more extreme and serious
when compared to those experienced by patients with non-heritable retinoblastoma.
Now that we have an understanding of the underlying cause, let's take
a look at the mechanism by which this disorder occurs.
To begin, let's understand the cell cycle
and its importance. The cell cycle is a series of
events that takes place in a cell to allow it
to divide. The cell cycle consists of five phases
g0 phase,
a G1 phase, a G2 phase, an S phase, and an M phase.
During the G1 phase, the retinoblastoma protein,
commonly referred to as pRB is bound to E2F,
a transcription factor.
A transcription is a protein that helps to regulate DNA
transcription.
The binding of pRB to E2F prevent E2F from binding
to DNA and transcribing genes.
The transcription of genes creates
proteins necessary for DNA replication.
When cells reach
the G1 checkpoint,
which occurs,
at the end of the G1 phase, they seek entry into the
S phase where DNA replication occurs. Prior to entry into the S phase,
E2F must bind to DNA and transcribe the
required genes needed to make proteins for DNA replication.
To set E2F
free,
pRB
needs to be inactivated.
This is accomplished by phosphorylating pRB. Phosphorylation refers
to the addition of phosphate groups to a protein.
The phosphorylation of pRB is accomplished by the
Cyclin-D/CDK4/6 complex.
This
complex adds phosphate groups to pRB and sets
E2F free from pRB. Thus, in this way,
E2F is able to bind to DNA and transcribe the
required genes.
In this way, the cell's
progression through the cell cycle is controlled.
However,
in the case of
retinoblastoma, the mutated RB1 gene
leads to the production of an abnormal pRB protein.
As a result pRB is not effectively able to bind to E2F.
E2F
in this case,
can continuously transcribe,
the genes needed for DNA replication and cells continuously move
through the cell cycle and rapidly divide. This ultimately leads
to the formation of tumours as seen in retinoblastoma.
Finally,
let's take a look at some treatment options. Treating
retinoblastoma depends on many factors,
some of which include the spread and location of the
tumour, and the stage of the tumour.
The ultimate goals are firstly to cure the
cancer as we don't want it to spread, followed by preserving vision as
much as possible.
For early-stage intraocular,
tumours, local treatments are typically used that interact with the
tumour itself.
These included cryosurgery, which is freezing and destroying the
tumour, thermotherapy and laser therapy,
which is heating and destroying the tumour, and radiation therapy, which is placing
radioactive material on the eye to treat the tumour.
These interventions are often done in conjunction with chemotherapy.
As the tumour grows larger and spreads,
the tumour may need to be removed by surgically removing
the eye itself.
This is known as an enucleation. Researchers continue to investigate
the optimal treatment regimes for retinoblastoma through large,
clinical trials
comparing the surgical and pharmaceutical interventions.
Following treatment, long-term
follow-up is necessary to monitor for potential recurrence of cancer.
Signs to look out for include new vision problems, headaches, or the presence of lumps or
swelling in the area.
We hope this video provided you with a greater understanding
of retinoblastoma.
Thank you for watching.
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